The 27-year-old toured New Zealand with the Lions four years ago, missing out on selection for the first Test but starting the second before injury prevented him from playing any part in the third international against the All Blacks.
The Pencoed product had been desperate to be part of a winning Lions set up this time around but is now playing down his chances of making Ian McGeechan's squad when it is announced on April 21.
"The injury will probably rule me out of the Lions tour," admitted Henson in an interview with BBC Sport.
"It'll be a pretty brave decision to take me now as I'm probably a bit of a liability with the way I am with my injures."
Henson's current ankle problem is just the latest in a long line of setbacks that has seen him struggle to play regular rugby since returning from the 2005 Lions tour.
He was an important of part of a second Grand Slam triumph in four years last season but injuries have prevented him from fully capitalizing on his enormous potential.
"This season is probably a miss now," added Henson.
"It is another difficult year. I've had an up and down last four years with injuries and I haven't been consistent at all - it has been tough.
"Then when I play in games the fitness isn't there because I haven't had a good run of games."
Gavin Henson made his Lions debut against Bay of Plenty in 2005
Henson's injury nightmare
Since returning from New Zealand with the Lions four years ago, Henson has spent time out with shoulder, knee, ankle, calf and Achilles tendon problems, as well as being handed a 10-week ban for elbowing Leicester's Alex Moreno in a Heineken Cup game at the Liberty Stadium in December 2005.
Henson returned from injury to feature in three Six Nations games this year
After missing all of his country's November internationals and the first two rounds of the Six Nations, Henson returned to Wales colours for the games against France, Italy and Ireland this spring.
Although he was on the losing side for the first time ever in the Championship in Paris, and then felt the pain of defeat once more against the Irish, Henson showed glimpses of the ability that convinced many onlookers that he was worthy of a place on the plane to South Africa.
However, another spell on the sidelines has left Henson not only questioning his Lions chances but also his rugby-playing career in general.
"It is hard to come back every time I'm injured. It is a complete nightmare again, I can't believe my luck. I'm pretty down and depressed about it at the moment, maybe I'm cursed.
"Everyone sees the press I get every time I get injured, it is tough for me and my family - it is hard to take.
"I still dream about good games but they are few and far between. I have probably started about eight games this season and the same last year and the year before that.
"It is pretty tough off the field, rugby has gone so professional you start to lose the enjoyment side of it. If all I am enjoying is playing then there is not much enjoyment then is there?
"There are more tough times ahead again. When I get knocked out with an injury, it is soul-destroying. Is it worth it?"
Henson scored twice against Southland prior to the second Test in New Zealand
Henson's time as a Lion in 2005
A star of Wales' first Grand Slam in 28 years, Henson traveled to New Zealand as one of the most-talked about players in the 45-man squad.
His 50-metre penalty kick against England had set Wales on their way to their Six Nations clean sweep and his all-round game had been lauded left, right and centre throughout the Championship.
A massive dump tackle on England debutant Matthew Tait had highlighted the physicality of Henson's defence, while his skills with ball in hand and his huge kicking game had been highlighted as key reasons behind his country's unexpected success.
Unfortunately for Henson, his first (and so far only) Lions tour did not go to plan. His absence from the first-Test defeat in Christchurch was one of the most-controversial non-selections of the entire tour and a picture of the then 23-year-old and head coach Sir Clive Woodward, that Henson says he was unaware was being taken, featured heavily in the national papers prior to the 21-3 reverse.
He did win a call up to the starting line up for the second Test after injury ruled out skipper Brian O'Driscoll, but Henson himself then suffered a similar fate as his Irish team-mate.
As well as being on the wrong end of a 45-18 thumping in Wellington, Henson was dealt a further blow as injury ended his own participation on the tour with just four appearances and one Lions Test cap to his name.
Having been 'devastated' to miss out on a place in the matchday 22 for the opening international and then seen injury prevent him from playing a part in the final rubber of the series, Henson left for home a disappointed man.
He vowed to do everything in his power to seek a change of fortunes in South Africa in 2009 but injury once again seems to have seriously hampered his chances of achieving that aim.
Henson's Lions stat attack
Three provincial appearances
June 4 Bay of Plenty Won 34-20
June 15 Wellington Won 23-6
June 21 Southland Won 26-16 Two tries
July 2 New Zealand 2nd Test Lost 45-18