Abstract：Objective：To observe the clinical effect of needle knife loosening tendon lesion combined with Xidian of hand point acupuncture on knee osteoarthritis(KOA). Methods： A total of 72 patients with KOA were randomly divided into the treatment group and the control group， with 36 cases in each group. The control group was treated with routine acupuncture，and the treatment group was treated with needle knife loosening tendon lesion combined with Xidian of hand point acupuncture. Both groups were treated for six weeks. Before and after treatment， the Chinese medicine syndrome scores，scores of Visual Analogue Scale(VAS) for knee joint pain，range of motion of knee joint，scores of Western Ontario and McMaster Universities Arthritis Index(WOMAC)，and levels of serum prostaglandin E2(PGE2) and β-endorphin(β-EP) in the two groups were compared. The clinical effective rates and incidence of adverse reactions in the two groups were compared. Results：The total effective rate was 94.12% in the treatment group，higher than that of 75.76% in the control group(P＜0.05). After treatment，the Chinese medicine syndrome scores in the two groups were decreased when compared with those before treatment(P＜0.05)； the Chinese medicine syndrome score in the treatment was lower than that in the treatment group(P＜0.05). After three weeks and six weeks of treatment，the VAS scores，scores of pain，stiffness，and difficulty of daily activities and total scores of WOMAC in the two groups were decreased when compared with those before treatment(P＜0.05)， and the range of motion of knee joint was larger(P＜0.05)； after three weeks and six weeks of treatment， the VAS score， scores of pain， stiffness and difficulty of daily activities and total score of WOMAC in the treatment group were lower than those in the control group at the same period(P＜0.05)，and the range of motion of knee joint was lager(P＜0.05). After treatment， the levels of serum PGE2 were decreased when compared with those before treatment(P＜0.05)， and the levels of β- EP were increased(P＜0.05)； after treatment， the level of serum PGE2 in the treatment was lower than that in the control group(P＜0.05)， and the level of β- EP was higher(P＜0.05). There was no significant difference being found in the comparison of incidence of adverse reactions between the two groups(P＞0.05). Conclusion： The therapy of needle knife loosening tendon lesion combined with Xidian of hand point acupuncture can significantly regulate the levels of PGE2 and β-EP in patients with KOA，effectively relieve the pain，increase the range of motion of joint and improve the Chinese medicine syndromes，knee joint function and clinical effects，with high safety.