Harrison split last season between the Steelers and the New England Patriots. Harrison returned to the Steelers in 2011.
This isn't the first time Harrison has hung up his cleats, but it's likely to have more finality than his initial flirtation with retirement.
During media availability at Super Bowl LII, Harrison said he was planning to return in 2018.
Pittsburgh signed the Kent State product in 2002 as an undrafted rookie free agent.
Harrison made the announcement on social media, saying he's "missed way too much for way too long ... and I'm done".More news: Los Angeles Police Seized Counterfeit Cosmetics Containing Animal Feces
With his career now over, Harrison can begin polishing up the speech he'll deliver in Canton, Ohio.
Father Time appeared to finally get the better of Harrison in 2017, though.
Harrison twice left the Steelers.
At a position where few last into their mid-30s, Harrison continued to thrive.
Harrison, who played most of his career with the Pittsburgh Steelers, briefly retired in 2014. He had two sacks in his debut with New England in the 2017 regular-season finale and added seven more tackles in the playoffs. He had 10 tackles, 3.5 sacks, three forced fumbles and an interception that day against Baltimore. The Ravens sent him to NFL Europe before eventually releasing him.