On December 26, 2017, Hughes signed a two-year contract with the Cincinnati Reds, with a $3 million club option or a $250,000 buyout for 2020. In his first season in Cincinnati, in 2018 Hughes posted a career-low 1.94 ERA (fourth-best in the majors among pitchers who threw at least 78 innings) and 1.017 walks plus hits per inning pitched during 72 appearances covering innings. He finished 4–3 with 7 saves.
