A seven-time Pro Bowler, Willis has missed the past three games for San Francisco (5-4) after injuring the toe in the third quarter at St. Louis on Oct. 13. He had 34 tackles and an interception this season for the Niners, who have reached the NFC Championship Game in each of the past three seasons.
Willis had hoped the injury wasn't so serious to sideline him long term. He missed practice last week after returning in a limited role the previous week.
After resting through the Oct. 26 bye, Willis was back as part of the 49ers' full active squad on the field for the start of practice Oct. 29, but he had been limited primarily to individual work.
Smith is set to begin practicing this week after serving his nine-game suspension by the NFL for violations of the league's substance-abuse and personal-conduct policies.
In addition, 2013 All-Pro NaVorro Bowman could be cleared to begin practice this week, opening a 21-day window for the team to activate him or place him on IR.
Bowman is recovering from surgery on his left knee after he tore the ACL and MCL in a devastating injury in the NFC Championship Game loss at Seattle last January.
Rookie Chris Borland has filled in for Willis and been spectacular, recording 18 tackles in a loss to the Rams two weeks ago then 17 more tackles in an overtime win at New Orleans on Sunday.
The Associated Press contributed to this report.