Taylor, last year's NFL rushing champion, will miss his second straight game with an injured ankle. He had missed only one game in his first two seasons, that one because he was considered a close contact during the COVID-19 pandemic.
Hines entered the concussion protocol since wobbling off the field last Thursday early in the victory at Denver.
The Jaguars (2-3), who beat the shorthanded Colts 24-0 in Week 2, will be without receiver Marvin Jones (hamstring) and defensive tackle Foley Fatukasi (quadriceps). Neither traveled with the team Saturday and both were downgraded from questionable to out.
"What we're looking for is consistency in performance," coach Frank Reich said Friday before decisions were made on Taylor and Hines. "We think Deon can provide that if needed. We feel like Deon took a major step [against Denver]. I don't think he surprised us. I think we felt he's had that in him."
Reich also announced Friday that three-time All-Pro linebacker Shaquille Leonard would sit out after having surgery on his broken nose. Leonard made his season debut two weeks ago against Tennessee but ran into teammate Zaire Franklin's face mask, which also caused a concussion.
Indy has lost four of six to the Jaguars. The Colts are a half-game behind Tennessee (3-2) in the division race but are 0-2-1 against AFC South foes.