Abstract： Objective： To observe the clinical effect of acupotomy for knee osteoarthritis(KOA) under the guidance of denervation theory. Methods：A total of 56 cases of KOA patients were selected and divided into the acupotomy group and the needling group according to the random number table method，28 cases in each group. The acupotomy group was treated with acupotomy under the guidance of denervation theory， and the needling group was given routine needling and electromagnetic hot lamp. Before treatment， after treatment， and during six- month follow- up， the scores of Visual Analogue Scale(VAS) of pain and Lysholm Knee Function Scale，as well as levels of interleukin-1β(IL-1β) and tumor necrosis factor- α(TNF- α) in serum were compared between the two groups. The adverse reactions were recorded. Results：After treatment and during six-month follow-up，the scores of VAS，claudication，joint interlocking，weight bearing，instability， pain，joint swelling and pain，going upstairs and downstairs，squatting and standing up in the acupotomy group were lower than those in the needling group in the same period(P＜0.05)，and levels of IL-1β and TNF-α in serum were lower(P＜0.05). During treatment，there was one case of local petechia and ecchymosis in both groups respectively，and due to the external application of compound sudium aescinate gel，the symptoms disappeared. During treatment，there was no fainting during acupuncture and local skin infection in the two groups. Conclusion：Under the guidance of denervation theory，acupotomy in the treatment of KOA can significantly relieve pain，improve the knee joint function，and reduce levels of IL-1β and TNF-α in serum，with high safety.