Abstract：Objective：To observe the clinical effect of the therapy of Guanjie Kebi Pills combined with western medicine on knee osteoarthritis (KOA) of cold-damp obstruction type. Methods：A total of 90 KOA patients were selected and divided into the control group and the study group according to the random number table method，with 45 cases in each group. The control group was given routine western medicine for treatment，and the study group was additionally treated with Guanjie Kebi Pills based on the treatment of the control group. The clinical effects，incidence of adverse reactions，and changes of levels of serum inflammatory factors [interleukin- 6 (IL-6)，interleukin-1β (IL-1β) and tumor necrosis factor- α (TNF-α)]， related indexes of Wntβ- catenin signal pathway in synovial fluid (levels of Wnt- 5a mRNA and β- catenin mRNA)，traditional Chinese medicine (TCM) syndrome scores，and scores of Visual Analogue Scale (VAS) of pain and Hospital for Special Surgery (HSS) were compared before and after treatment between the two groups. Results：The total clinical effective rate was 93.33% in the study group and 77.78% in the control group，the difference being significant (P＜0.05). After treatment，the levels of IL-6，IL-1β and TNF-α in the two groups were decreased when compared with those before treatment (P＜0.05)， and the above three levels in the study group were lower than those in the control group (P＜0.05). After treatment，the levels of Wnt- 5a mRNA and β- catenin mRNA in the study group were significantly decreased when compared with those in the control group，the difference being significant (P＜0.05). After treatment，the TCM syndrome scores and VAS scores in the two groups were decreased when compared with those before treatment (P＜0.05)， and the HSS scores were increased when compared with those before treatment (P＜0.05)；the TCM syndrome score and VAS score in the study group were lower than those in the control group (P＜0.05)， and the HSS score was higher than that in the control group (P＜0.05). The incidence of adverse reactions was 6.67% in the study group and 11.11% in the control group，there being no significance in the difference (P＞0.05). Conclusion： The therapy of Guanjie Kebi Pills combined with western medicine can improve the curative effect on KOA and clinical symptoms，with great safety.