Molinari led by two shots after the first round, and following a slow start Friday he closed with three birdies across his final five holes. At 10 under, he leads by two shots over Argentina's Emiliano Grillo.
Molinari was a runner-up last week at the Open de Espana and feels comfortable at Wentworth. He has cracked the top 10 each of the last three years at this event, including a T-7 finish last year. He has reached 31 of 36 greens in regulation through the first two rounds this week.
"I just enjoy playing around here," Molinari said after a 65 in the opening round. "I always have, and hopefully I always will."
Molinari was one of the last players to gain entry into the WGC-Cadillac Match Play Championship earlier this month, and he enters this week at No. 66 in the world with a pair of OWGR cutoffs looming. The top 60 players after this week will gain entry into the U.S. Open, while the top 50 will also earn berths in the Open Championship at St. Andrews.
Molinari has yet to qualify for either event, and he is eager to get back into the majors after missing the Masters for the first time since 2009.
"I know the deadline for the U.S. Open and the Open are close, and it would mean a lot to have a good week here," he said. "All season I've been pretty much just outside the top 50, knowing that a good week would get me in again. So it's not too different from how I was feeling the rest of the season."