Folau is uncapped at Test level in rugby union, while O'Driscoll has made 125 Test appearances for Ireland and six more for Britain and Ireland's elite, with only George Gregan and Ronan O'Gara more experienced on the global stage.
Former rugby league international Folau only made the switch from Australian Rules Football to union at the start of the southern hemisphere season but has already shown enough talent to win a place in Robbie Deans' Qantas Wallabies squad for the three-Test series, which starts a week on Saturday.
Gaffney has seen the 24-year-old's progression both in training and in competitive action over the past four months and he is confident that the utility back can cause The Lions plenty of problems.
"He's a good footy player, he's a great athlete and he's got a great sense of the game," said Gaffney, who would like to see Folau start at full back rather than on the wing, with Kurtley Beale at fly-half and James O'Connor out wide.
"At 15 for us, he's been outstanding. He obviously took a little while to get into it, but not too long.
"I'd love to see him at 15 for Australia. It's a lot easier for Issy to come into the game playing at 15, because he's got a lot more space.
"He's scored eight tries in our season, which is not a bad performance in his first year. I'd love to see him given space and time.
"I'd play (Kurtley) Beale at 10. He's had problems I know but going forward Kurtley at 10 is the answer for me. As an individual that's what I'd do. I don't think they'll pick the side that I would, but they're probably looking for different things than I'd be looking for.
"He (Kurtley) controls the game a lot better, in my personal opinion. (James) O'Connor is the man they're talking about and he's an excellent rugby player, there's no doubt about it. I'd just rather see him with space out wide where he handles the game better. I'd have O'Connor in the XV but I think Kurtley controls the game better."
As for O'Driscoll, Gaffney coached the veteran centre during his time with Leinster and with Ireland and he sees no reason why the 34-year-old can't repeat his Lions heroics from 2001.
O'Driscoll was one of the standout performers on the last Lions adventure in Australia and Gaffney is predicting more of the same this time around.
"It's been great to see Drico play particularly well in the time he's had on the paddock," added Gaffney.
"It looks like he's maturing and getting better!
"I thought he played extremely well last night (against the Combined Country XV). The opposition wasn't great but you can only do what you can do.
"From what I've seen, he's been very, very good. He took a knock but won't play on Saturday.
"I just hope he makes the Test team. (Jamie) Roberts will be the 12 but his (O'Driscoll's) form so far on tour means he'll be very hard to leave out of the Test side."
Gaffney has been impressed with what he's seen of The Lions in their four tour matches to date but he is keen for his own players to give Warren Gatland's men a real test in Sydney this weekend.
The Waratahs may be struggling with injuries and international call ups but the availability of halfbacks Bernard Foley and Matt Lucas is a boost, with Gaffney hoping some of the less heralded players in his squad will step up the plate, just as they did when they won 28-13 at the Force on Sunday.
"The Lions have looked very strong. I've been pretty impressed. Obviously they're still getting their combinations together…by the time they get to the first Test, they'll be well primed.
"It's a pity that we've got so many missing on Saturday. It's not by our doing, it's just the way's it's happened.
"We've got 10 in the Wallaby squad, we've got two more who would be in the squad in (Sitaleki) Timani and (Tatafu) Polota-Nau, and we've got four out with long-term injuries. But we've still got some good players. We've got 16 guys who would be in our top 23 out but it gives other guys an opportunity.
"We went up against the Force last week, against their top side, and we were supposed to get flogged and we dished them up pretty easily. We'll put up a battle for sure."