Abstract：Objective：To observe the clinical effect of modified Bugan Yishen Decoction combined with western medicine on senile knee osteoarthritis （KOA）. Methods： A total of 148 senile KOA patients admitted to Dongyang Garden Tian′s Hospital from January 2021 to February 202 were randomly divided into the control group and the treatment group， with 74 patients in each group， using a random number table method. Both groups were given functional rehabilitation exercises. The control group was treated with Celecoxib Capsules and Vitamin A and D Soft Capsules，while the treatment group was treated with modified Bugan Yishen Decoction based on the treatment of the control group. Both groups were treated continuously for eight weeks. Compared the symptom and sign scores， Harris scores， Visual Analogue Scale （VAS） scores， 6-Item Short Form Health Survey （SF-6） scores， and Toll-like receptor（ TLR） 2，TLR4，and myeloid differentiation factor 88（ MyD88） levels before and after treatment between the two groups， and evaluated the clinical efficacy and incidence of adverse reactions between the two groups. Results： During the treatment process， one case fell out of the treatment group and four cases fell out of the control group. Ultimately， 7 cases were completed in the treatment group and 70 cases were completed in the control group. After treatment， the total effective rate was 95.89% （70/7） in the treatment group， which was higher than that of 84.29% （59/70） in the control group （P＜0.05）. After treatment， the symptom and sign scores， VAS scores， and knee joint fluid TLR2， TLR4， and MyD88 levels in both groups were decreased when compared with those before treatment （P＜0.05），while Harris scores and SF-6 scores were increased （P＜0.05）；the Harris score and SF-6 score in the treatment group were higher than those in the control group （P＜0.05），while the symptom and sign scores， VAS score， and knee joint fluid TLR2， TLR4， and MyD88 levels were lower than those in the control group （P＜ 0.05）. Both groups did not experience any adverse reactions. Conclusion：The combination of modified Bugan Yishen Decoction and western medicine has significant clinical efficacy in treating senile KOA patients. It can alleviate clinical symptoms and pain， improve knee joint function， and its mechanism of action is related to the inhibition of TLRs/ MyD88 pathway.