OBJECTIVE: To observe therapeutic efficacy and safety of Duhuo jisheng decoction combined with glucosamine gulfate for genual osteoarthritis. METHODS: Totally 86 patients with genual osteoarthritis selected from our hospital during Dec. 2015-Apr. 2016 were divided into trial group and control group according to random number table, with 43 cases in each group. Control group was given Glucosamine sulfate tablets 1-2 tablet, po (at mealtime), tid. Trial group was additionally given Duhuo jisheng decoction, one dose a day, decocting 200 mL with water, morning and evening at twice, on the basis of control group. Both groups received treatment for 28 d. Clinical efficacies of 2 groups were observed as well as the levels of hs-CRP, TNF-α, IL-6, MMP-3, MMP-9 and MMP-13. The occurrence of ADR was recorded during treatment. RESULTS: Before treatment, there was no statistical significance in hs-CRP, TNF-α, IL-6, MMP-3, MMP-9 and MMP-13 between 2 groups (P>0.05). After treatment, total response rate of trial group (95.3%) was significantly higher than that of control group (76.7%), with statistical significance (P<0.05). The level of hs-CRP in trial group was significantly lowered, and the levels of TNF-α and IL-6, MMP-3, MMP-9, MMP-13 in 2 groups were decreased significantly; above indexes of trial group were significantly lower than those of control group, with statistcal significance (P<0.05). The incidence of ADR in trial group (7.0%) was significantly lower than control group (46.5%), with statistical significance (P<0.05). CONCLUSIONS: Duhuo jisheng decoction combined with glucosamine gulfate shows good therapeutic efficacy for genual osteoarthritis with good safety.