Abstract： Objective： To observe the clinical effect of Gubing Huisheng Pills combined with sodium hyaluronate for knee osteoarthritis(KOA)， and its effect on serum 25 hydroxyvitamin D and N- terminal/ midregion(N-MID). Methods：A total of 80 patients with KOA were divided into the control group and the observation group according to the random number table method，with 40 cases in each group. The control group was treated with sodium hyaluronate， and the observation group was additionally treated with Gubing Huisheng Pills based on the treatment of the control group. Before and after treatment， the traditional Chinese medicine(TCM) syndrome scores， scores of Visual Analogue Scale(VAS)， Western Ontario and McMaster Universities Arthritis Index(WOMAC) and Lysholm Knee Scale(Lysholm)，as well as levels of serum 25 hydroxyvitamin D and N- MID were compared between the two groups. The clinical effects in the two groups were evaluated. Results： After treatment， the scores of pain and feelings of heaviness and adhering of joint，inhibited flexion and extension of joint and heavy pain of lumbus in the two groups were decreased when compared with those before treatment(P＜0.05)，and the above three scores in the observation group were lower than those in the control group(P＜0.05). After treatment，the scores of VAS and WOMAC were decreased when compared with those before treatment(P＜0.05)， and the scores of Lysholm were increased(P＜0.05)；the scores of VAS and WOMAC in the observation group were lower than those in the control group(P＜0.05)， and the score of Lysholm in the observation group was higher than that in the control group(P＜0.05). After treatment， the levels of serum 25 hydroxyvitamin D and N-MID in the two groups were increased when compared with those before treatment(P＜0.05)，and the above two levels in the observation group were higher than those in the control group(P＜0.05). The total effective rate was 92.50% in the observation group，higher than that of 80.00% in the control group (P＜0.05). Conclusion：Gubing Huisheng Pills combined with sodium hyaluronate for KOA can improve the clinical symptoms and knee joint function，regulate the levels of serum 25 hydroxyvitamin D and N-MID.