Despite the tough matchup, the Tigers may be able to snap their losing streak based on the White Sox's own struggles in Quintana's starts.
Detroit looks to avoid losing a fourth in a row and continue its home dominance of Chicago in Tuesday night's series opener.
The AL Central-leading Tigers (57-45) have dropped eight of 12, and plated two runs while batting .141 in losing the final three contests of a four-game series against the Los Angeles Angels. They managed one baserunner after the first inning of Sunday's 2-1 defeat.
Cleanup hitter Victor Martinez is batting .229 with two extra-base hits in the last 10 games, and J.D. Martinez has cooled off considerably, going 3 for 26 in his last eight to drop his average 27 points to .317.
"Teams go through offensive slumps," manager Brad Ausmus said. "It happened early in the season, and it'll probably happen again during the season.''
The slump may very well continue against Quintana (5-7, 3.45 ERA), who has limited opponents to a .188 batting average in his last seven starts.
He has a 1.70 ERA with 49 strikeouts over 47 2-3 innings in that span, but is just 2-0. The White Sox are 3-7 in his last 10 starts, backing Quintana with an average of 1.97 runs.
Chicago lost again behind Quintana on Wednesday, falling 2-1 to Kansas City despite the left-hander's seven innings of one-run ball.
Quintana hasn't faced the Tigers since making back-to-back starts against them at the end of April. He yielded three runs over six innings in each.
Miguel Cabrera went 3 for 6 off Quintana in those games and is 5 for 12 with a homer in their matchups since 2013.
Austin Jackson is 2 for 13 against Quintana since 2013, but has been one of the few bright spots in Detroit's lineup, hitting .397 over his last 16 games.
Cabrera was batting .405 over a nine-game stretch before going hitless in the final two contests in Anaheim. He is batting .359 with two homers and nine RBIs in nine games against Chicago this season, helping Detroit to five wins.
The reigning two-time AL MVP is hitting .446 with 19 RBIs in his last 17 home games against the White Sox, and the Tigers have won 26 of the last 34 meetings in Detroit.
Although Chicago (51-55) failed to sweep a four-game set from Minnesota after Sunday's 4-3 loss, manager Robin Ventura was pleased his team scored 21 runs in the three wins.
"It's nice to get some under our belt here," Ventura told MLB's official website. "We know we've got a tough series coming up."
Rookie star Jose Abreu is batting .371 with eight doubles during a 17-game hitting streak and has hit safely in 35 of 36. He is batting .306 with four homers and four doubles versus Detroit and doubled in one of three at-bats against Anibal Sanchez (7-4, 3.45).
Sanchez had another rough outing Wednesday in Arizona, permitting five runs and a season-high 11 hits in 6 1-3 innings, but was bailed out by his offense in an 11-5 win. Excluding a solid showing in beating Kansas City on July 11, the right-hander has an 8.00 ERA in his other three starts this month. He entered July with a 2.63 ERA.
In his only 2014 outing against Chicago on April 21, Sanchez gave up three runs in 6 1-3 innings of a 3-1 loss.