The duo, who have twice toured together with the Lions will come face to face in the Celtic rival's penultimate RBS 6 Nations clash.
The pair are also embroiled in their own personal battle to break Ian Smith's Championship record of 24 tries. While O'Driscoll currently stands on 23, Welsh speedster Williams is hot on the heels with 22.
But 32-year-old O'Driscoll insists he is not interested in personal accolades but intent on keeping Williams under wraps.
"I think Wales really tick when Shane is playing well for them," said O'Driscoll.
"He gets his hands on the ball a hell of a lot more than most international wingers and he has big moments in big games for them.
"He's scored over a half century (52) of tries in 70 something (78) Test matches, which is a fairly impressive strike rate.
"Look at that alone and I don't think you have to be a genius to work out they're going to get the ball into his hands and create trouble for us defensively."
O'Driscoll is also wary of the threat posed by his Lions midfield partner Jamie Roberts.
"He's a talented footballer, a great ball-carrier, a big, hard, physical guy and he uses his size really well," said the 110-times capped Irish great.
"Jamie's the sort of guy who accelerates into tackles. He knows the power he possesses, so he's definitely a player of a very good calibre and getting better with the more Test matches he plays.
"So, yes, he's a big threat."
And O'Driscoll has revealed that any old friendships forged during previous Lions tours would be banished for 80 minutes come kick-off on Saturday.
"You see them in a very different light when they're your own team-mates," added the 2005 Lions captain.
"It's the same as playing provincially against your own team-mates in Ireland. You shelve everything for 80 minutes and normality resumes after that.
"There won't be too much pally-pally on the pitch."