Willis' injury is not considered serious but the team will proceed with caution to allow time for the hand to heal, sources said. He has suffered previous fractures to the same hand.
Barely 45 minutes into Thursday's workout, the 49ers suffered another injury when trainers carted cornerback Chris Culliver off the field with an apparent left knee injury. He was covering a punt in a non-contact drill when he went down in pain. He held his left knee and buried his head in his hands before being taken off the field.
A league source told ESPN NFL Insider Adam Schefter that Culliver suffered a torn ACL.
Willis was wearing a black cast around the base of his right hand and wrist Thursday and not participating in practice.
The nature of Willis' injury had been earlier reported by ProFootballTalk.com.
Willis, 28, suffered the injury during one-on-one blocking drills Wednesday and watched the rest of practice from the sideline with his wrist heavily wrapped.
He walked off the field smiling with linebacker NaVorro Bowman, who just sat out team drills with a groin injury that kept him out of all of Tuesday's practice.
A Pro Bowl selection in each of his six NFL seasons, the linebacker has recorded more than 100 tackles in five of his six seasons, including 120 in 2012.
Coach Jim Harbaugh and players looked on as trainers attended to Culliver. General manager Trent Baalke consoled Culliver by putting his arm around the cornerback before he was carted off the field. Harbaugh said Culliver will undergo an MRI.
Culliver had 47 tackles, two interceptions and one forced fumble last season while playing primarily as the team's third cornerback. He was drafted in the third round out of South Carolina in 2011.
"What it means right now is there are some guys getting an opportunity to show what they can do, which is a positive there. And there's people who have been doing that," Harbaugh said.
New cornerback Nnamdi Asomugha already had been taking plays away from Culliver in practice. Tramaine Brock and Cox will be expected to carry more of a load as well if Culliver is out for an extended period.
Information from ESPN NFL Insider Adam Schefter and The Associated Press was used in this report.