Harris' 68 career touchdown passes rank fourth all-time in the conference's record book and are eight fewer than former North Carolina State quarterback Russell Wilson, who sits in third place with 76.
Harris will be lining up Saturday against one of the toughest defense he's seen this year.
Florida State (6-3, 4-2 ACC) ranks fourth nationally in total defense and the Seminoles' 30 quarterback sacks lead the ACC.
''They're the most talented defense that we face this year,'' first-year Miami coach Al Golden said. ''This will be our greatest test, irrespective of the rivalry or the series.''
Miami offensive line coach Art Kehoe has been around for many games in the series and said his troops have a ''massive challenge'' Saturday in protecting their quarterback.
''They're coming after your passer,'' Kehoe said. ''That's what they're about.''
Golden is also concerned about Florida State's depth on defense.
''Just the number of guys that they play on the defensive line and then the second wave comes in and they're as effective as the first wave,'' Golden said. ''Very skilled and quick lateral movements to get around you.''
Harris is returning to the site of one of his best performances. The 6-foot-4 quarterback threw for 386 yards and two touchdowns and ran for another in Miami's 38-34 victory over Florida State on the Seminoles' home field in 2009.
The Seminoles will also have to deal with Miami running back Lamar Miller, who is second in the conference in rushing with 1,016 yards.
Both teams have plenty of talent offensively and have had little problem scoring points.
Florida State is averaging 35.9 points a game and has scored 30 or more points in its last six games while Miami averages 30.7 points and hung 35 on 10th-ranked Virginia Tech in a losing effort.
Florida State junior quarterback E.J. Manuel, who ranks 12th nationally in pass efficiency and second in the conference in total offense, is also getting back his most dangerous deep threat in time for Saturday's kickoff. Freshman Rashad Greene is second on the team with 26 catches for 457 yards and leads with six TD catches despite missing the last four games with an ankle injury.
Receiver Rodney Smith leads the Seminoles with 28 catches for 486 yards. The 6-5 junior has three touchdown catches.
Miami has its own 6-5 receiver in Tommy Streeter, who has caught 32 passes for 666 yards and eight touchdowns.
Florida State has won four straight since a three-game losing streak early in the season knocked them out of the national polls and most likely any chance of playing in the ACC title game next month. Clemson can lock up the Atlantic Division crown with a win Saturday over Wake Forest.
Fisher is hoping the Seminoles have retained the momentum built over the past month with easy victories over Duke, Maryland, North Carolina State and Boston College by a combined 154-39.
''We're learning how to take care of what we're supposed to take care of on a daily basis,'' he said.
The Seminoles are defending state champions with wins over the Hurricanes and Florida and would like to repeat. They finish the season at Florida in two weeks.
''It's about bragging rights,'' said Florida State defensive back Lamarcus Joyner, who is from Miami. ''That's what's going to make this game that much more fun.''