Objective To explore the clinical efficacy of Xiaozhonghuayu ointment in the treatment of osteoarthritis．Methods From May 2017 to January 2022,124 patients with osteoarthritis who diagnosed and treated in our hospital were selected as the research subjects．According to the simple allocation principle,the patients were divided into the Xiaozhonghuayu ointment group and the traditional medicine group with 62 cases each．The traditional medicine group was treated with traditional medicine,and the Xiaozhonghuayu ointment group was treated with Xiaozhonghuayu ointment．The total therapeutic efficiency,pain score,joint score,and the changes of serum inflammatory factors were compared in the two groups．Results The total efficiency of Xiaozhonghuayu ointment group after treatment were 98.4%,which were higher than 83.9% in the traditional medicine group（P<0.05）．The pain scores in both groups after treatment were lower than those before treatment（P<0.05）,and that in the Xiaozhonghuayu ointment group were lower than the traditional medicine group（P<0.05）．The joint scores of the two groups after treatment were higher than those before treatment（P<0.05）,and that in the Xiaozhonghuayu ointment group were higher than the traditional medicine group（P<0.05）．After treatment,the levels of serum interleukin-1β and interleukin-6 in the two groups were significantly lower than those before treatment（P<0.05）,compared with the traditional medicine group,those levels in the Xiaozhonghuayu ointment group also decreased significantly after treatment（P<0.05）．Conclusions Xiaozhonghuayu ointment in the treatment of osteoarthritis can effectively inhibit the expressions of serum inflammatory factors,promote pain relief,improve joint function,and improve the overall therapeutic effect of patients．