O'Driscoll - a certainty to at least tour with the Lions in the summer - returns to the Irish side after he missed the comprehensive victory over Scotland in Edinburgh last time out because of a hamstring injury.
The return of the Ireland captain to the midfield will give his team an outstanding chance of recording a third successive win in this season's tournament and keep Ireland on course for a possible first Grand Slam since 1947.
England, in contrast, have lost eight of their last 11 Tests, and will find themselves in the unfamiliar position of rank outsiders.
They will inevitably afford centre O'Driscoll close attention, given his supreme game-breaking qualities, but he is fully prepared for the soccer equivalent of being man-marked.
"The more I play, the more I realise there is more pressure," he said.
"The space will not always be there for me, and I have to look to put others through the gaps. It is a team game, and you are not looking for headlines."
Expectancy among Irish fans is huge as their heroes look to avenge a 42-6 thumping when England last visited Dublin for a Grand Slam showdown two years ago.
"From the public's point of view, it doesn't get much bigger than Ireland v England," O'Driscoll added.
"Two years ago, England showed their class, and last year at Twickenham, we were the better side. Both teams are in a pressure situation, with us looking for a third win in a row and England looking for their first victory."