To assess for any additive value of hydroxychloroquine (HCQ) in Japanese patients with systemic lupus erythematosus (SLE) depending on calcineurin inhibitors (CNIs). We retrospectively evaluated patients with SLE who visited our hospital from 2015 to 2016 and were taking prednisolone (PSL) at <20 mg/d and one immunosuppressant (IS). Patients were divided into two groups depending on HCQ use and the groups were compared for changes in SLE Disease Activity Index (SLEDAI), prednisolone (PSL) dose, and cumulative flare rate between patients who were treated and not treated with CNI. Among the 103 patients evaluated, 19 (18.4%) were treated with HCQ. On analysis of all patients, SLEDAI, PSL doses, and cumulative flare rate were significantly reduced in patients who received HCQ compared to those who did not (P = 0.04, P = 0.01, and P = 0.03, respectively). Regarding IS use, we found less additive therapeutic effect in CNI users than in users of other ISs in terms of reduction in SLEDAI and PSL dose (P = 0.05 and P < 0.01, respectively). The addition of HCQ reduced disease activity, PSL dose, and flares in Japanese SLE patients but conferred less additive clinical efficacy when added to CNIs. © 2018 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.