The Lions have to win at Loftus to keep the three Test Castle Series alive and O'Driscoll believes the men in red can take plenty out of their defeat in the first Test to give them a chance of squaring the series.
"You're always confident when you're playing in a Lions team and some of the rugby we played last weekend showed we have the confidence to play the game we want to," said O'Driscoll, who will be winning his sixth Lions Test cap.
"We have to bring that out from the kick-off this weekend because we can't afford to give them a 19 point lead and chase it back. We probably didn't play early enough last weekend and that was to our detriment.
"We need to start playing earlier in the first half this time, cut off the Springboks and make them work for their scores a little bit more than we did last weekend. We were obviously hopeful of winning in Durban, but it's done now and we are out to win Tests two and three - it's as simple as that."
As well as taking on John Smit's world champions with their noses in front in the series, the Lions also have to travel from sea level in Cape Town up to altitude in Pretoria to try to level things up. That is bound to make their task harder, although O'Driscoll isn't worried about the effects.
"Hopefully it won't have a negative impact. There's a difference between playing at sea level and playing at altitude, but we've played at altitude for the first three games of the tour and we know what it takes," said O'Driscoll.
"We're just looking forward to pushing our bodies, particularly in the second half when you start feeling the effects of it."