Pochettino's Tottenham will welcome quadruple-chasing Premier League rivals City to their new stadium for Tuesday's opening leg.
City have already won the EFL Cup as they look to add the Premier League, Champions and FA Cup to this season's haul.
"Yes – as a coach, yes," Pochettino replied when asked if his first Champions League quarter-final was the biggest game of his life.
"For us it's a bonus to be here, to have the possibility to play in the quarter-finals with all the circumstances, and the objective is to be in the semi-final."
"City are a very, very good team and it's going to be tough, the games against him... sorry, them," Pochettino said.
"We need to start being tough and aggressive, put a high tempo on the game and hope the atmosphere will be tough for our opponents."
In the Premier League, Spurs currently sit in fourth place behind Chelsea, although the club currently has an extra match to play following the Blues 2-0 win over West Ham on Monday.
Tottenham recently opened the club's brand new stadium, having defeated Crystal Palace 2-0 to open the new venue.
After taking on Manchester City, Spurs will take on Huddersfield Town before heading to the Etihad for the second leg of their Champions League clash.