Ephron died of leukemia last year at the age of 71.
She and Hanks had previously worked on the romantic comedy classics "Sleepless in Seattle" and "You've Got Mail."
The New York Post said the two-time Oscar-winning actor struggled to hold back tears as he enjoyed a standing ovation at Monday's opening night of "Lucky Guy."
"That was a tough moment. We were going to do this, and Nora and [show director] George C. Wolfe were going to walk out onstage. I miss her. What more can you say?" Hanks told the Post after the performance. "Nora was just a magnificent hang ... You could be working, and you could be talking about personal things. You could be on vacation and talking about cultural history. You could be having a very lazy breakfast and you would be talking about Saddam Hussein. Nora was ... fascinated by everything. She was always doing things that were so interesting. She told me, 'Never turn down a front-row seat for human folly.'"