He finished the regular season with 87 combined tackles, 9 pass deflections, 3½ sacks, and 3 interceptions in 12 starts and 13 games. On January 8, 2017, Shazier recorded six combined tackles and intercepted Matt Moore, as the Pittsburgh Steelers defeated the Miami Dolphins in the AFC Wildcard game 30–12. On January 15, 2017, he recorded 5 combined tackles and intercepted Alex Smith in the Steelers' 18–16 Divisional Round victory over the Kansas City Chiefs.
On April 24, 2017, the Steelers picked up the fifth-year option on Shazier's contract.
On September 10, 2017, Shazier had one of the best statistical games of his career, tying a career-high with 11 solo tackles and forcing a career-high of two forced fumbles during a 21–18 victory over the Cleveland Browns.
During a Monday Night Football game against the Cincinnati Bengals on December 4, 2017, Shazier sustained what appeared to be a severe back injury after a head-on tackle. The hit left Shazier seemingly unable to move his legs. After stabilization he was taken to the hospital and the next morning revealed that he had sustained a spinal contusion. On December 7, Shazier underwent spinal stabilization surgery to secure the injured section of spine and to aid in his recovery. The surgery ended his 2017 season. But despite the injury, Shazier was named to his second Pro Bowl on December 19, 2017. He was ranked 47th by his peers on the NFL Top 100 Players of 2018.
Shazier has alopecia, an autoimmune condition which prevents the growth of hair on the body. Throughout his childhood, he was the subject of ridicule and taunting because of this. However, with support and encouragement from his parents, Shazier developed an altruistic temperament to deal with the jabs and name calling. In May 2017, he wrote of his experiences when his hair unexpectedly began growing back.