Symptoms of hand osteoarthritis result in activity limitations and lower quality of life. Hydroxychloroquine, which has been used successfully in the treatment of many autoimmune diseases, can suppress inflammation and might also be beneficial in hand osteoarthritis. We plan to perform a systematic review and meta-analysis of randomized clinical trial to determine the symptom-modifying effect of hydroxychloroquine in hand osteoarthritis. We will search PubMed, EMBASE, Cochrane Library, and Web of Science using a comprehensive strategy. The related conference proceedings and reference lists of the included studies will also be checked to identify additional studies. Two reviewers will screen retrieved records, extract information and assess the risk of bias independently. Stata v15.1 software will be used to conduct data synthesis. This study will be submitted to a peer-reviewed journal for publication. We hope it will provide a relatively comprehensive reference for clinical practice and future relevant clinical trials. INPLASY2020110005.