The home favourite came through a potential banana skin in the first round by dispatching talented Russian Daniil Medvedev in straight sets and will feature on Philippe Chatrier once again.
Pouille had some success in the early part of the season and won an ATP 250 event in February, but his results on the clay had been very disappointing before that first round win.
Last year's run to the third round represents his best performance at the French Open so the world number 16 will at least want to eclipse that with victory here.
British number three Norrie benefitted from Peter Gojowczyk retiring with injury in the first round but he was leading 6-1, 2-0 and in full control when that occurred.
Speaking after his French Open debut, Norrie himself has claimed that he was playing "the best tennis of his life" up until his opponent conceded the match.
The 22-year-old - who recently broke into the top 100 for the first time - is relishing his underdog status against Pouille and been quick to point out that all the pressure will be on the Frenchman.
In one of the ties of the second round, up-and-coming British hope Cameron Norrie will take to the Phlippe Chatrier stage against the top-ranked Frenchman in Lucas Pouille. With home support and greater experience at the top level, Pouille goes in as the bookies' favourite but he may not have it all his own away against an opponent full of confidence and with nothing to lose.
Expect a tight match here and don't be surprised if this goes the full five sets with Norrie in with a fighting chance of causing an upset.