Objective To study the therapeutic effect of acupotomy and manual release on intractable pain of knee osteoarthritis （KOA） in early and middle stages. Methods A total of 80 patients with intractable pain of KOA in early and middle stages from January 2023 to January 2025 were selected and randomly divided into a control group （40 cases） and an observation group （40 cases）. The control group was treated with acupotomy alone, while the observation group was treated with acupotomy and manual release. The pain indicators, knee joint function, treatment effect, inflammatory factors, adverse reaction incidence, and recurrence between the two groups were compared. Results After treatment, the pain indicator scores and knee joint function scores of the observation group were lower than those of the control group （P<0.05）, the effective rate of treatment was higher （P<0.05）, the inflammatory factor levels were lower （P<0.05）, and the recurrence rate was lower （P<0.05）, but there was no difference in the adverse reaction rate between the two groups （P>0.05）. Conclusion The combination of acupotomy and manual release can safely and effectively treat intractable pain of KOA in early and middle stages, improve pain symptoms and joint function, inhibit inflammatory reaction, and reduce the recurrence rate of the disease.