Background: Hand eczema (HE) refers to a common inflammatory dermatological condition. Several studies have shown that statins may have anti-inflammatory effects. This study aimed at investigating the efficacy of adding topical atorvastatin to topical betamethasone in the treatment of chronic HE. Methods: This randomized, double-blind, placebo-controlled research was done between October 2017 and August 2018 in Hamadan, Iran. Of 130 cases treated for HE, 88 were randomly assigned to groups receiving either betamethasone 1% ointment plus atorvastatin 5% cream (n = 44) or betamethasone 1% ointment plus vehicle cream (n=44). Both groups applied their medications twice a day for 10 days. The primary outcome was changes in the severity of HE, assessed by hand eczema severity index (HECSI). The secondary outcomes were changes in itching evaluated via visual analogue scale (VAS) and quality of life examined through dermatology life quality index (DLQI). Results: Seventy-two out of 88 eligible cases completed the study. The mean HECSI scores decreased in both groups after the intervention, although the change in HECSI was greater in the atorvastatin group (adjusted mean difference [AMD]: 5.756; 95% CI: 5.168 to 6.344, P<0.001). The mean VAS scores decreased in both groups after the intervention, although the change in VAS was greater in the atorvastatin group (AMD: 10.535; 95% CI: 7.005 to 14.064, P<0.001). Treatment with topical atorvastatin was more effective in improving DLQI (AMD: 1.990; 95% CI: 1.821 to 2.158, P<0.001). Conclusion: Addition of topical atorvastatin to topical betamethasone is beneficial in treatment of chronic HE. Trial Registration: Identifier: IRCT2017070922965N10; https://www.irct.ir/.