Ephron wrote and directed two of Hanks' biggest hits -- "Sleepless in Seattle" and "You've Got Mail."
Helmed by George C. Wolfe, "Lucky Guy" will play a limited engagement at the Broadhurst Theatre, with an opening night planned for April 1.
Previews will begin March 1 and additional casting is expected to be announced in coming weeks.
The play is set in the "scandal- and graffiti-ridden New York of the 1980s, as told through the story of the charismatic and controversial tabloid columnist Mike McAlary," a synopsis said. "From his sensational reporting of New York's major police corruption to the libel suit that nearly ended his career, the play dramatizes the story of McAlary's meteoric rise, fall and rise again, ending with his coverage of the Abner Louima case for which he won the Pulitzer Prize, shortly before his untimely death on Christmas Day 1998."
Hanks will play McAlary in "Lucky Guy." His film credits include "Splash," "Forrest Gump," "Philadelphia," "Apollo 13," "Saving Private Ryan," "Cast Away," "The Da Vinci Code," "Angels & Demons" and the upcoming "Cloud Atlas."
Ephron died this year of cancer. She was 71.