Objective:To study the clinical efficacy of orthopedics No.1 prescription combined with celecoxib in the treatment of knee osteoarthritis （KOA） with middle stage of cold-dampness syndrome and investigate its effect on serum cytokines levels. Method:The 72 patients were randomly divided into control group and observation group， with 36 cases each. Patients in both groups were given basic treatment with oral celecoxib capsules （0.2 g/ time， 1 time/day）. On the basis of western medicine treatment， patients in observation group were treated with orthopedics No.1 prescription decoction-free granules by fumigation， 1 bag/time， 1 time/day， 5 times/week. Both groups received treatment for 4 weeks. The visual analog pain score （VAS）， American knee society knee score （KSS）， serum interleukin-1<italic>β </italic>（IL-1<italic>β</italic>）， tumor necrosis factor-<italic>α </italic>（TNF-<italic>α</italic>）， and transforming growth factor-<italic>β</italic>₁（TGF-<italic>β</italic>₁） levels were observed before and after treatment， and their clinical efficacy was evaluated. Result:After treatment， VAS score significantly decreased in both groups （<italic>P</italic><0.01）， and KSS score significantly increased （<italic>P</italic><0.01）， with better clinical effect in observation group. After treatment， serum IL-1<italic>β</italic> and TNF-<italic>α</italic> levels decreased significantly in both groups （<italic>P</italic><0.01）， and the levels in observation group were lower than those in control group after treatment （<italic>P</italic><0.05）. TGF<italic>-β</italic>₁content was significantly higher than that before treatment in two groups （<italic>P</italic><0.01）. Conclusion:Orthopedics No.1 prescription combined with celecoxib for the treatment of KOA with middle stage of cold-dampness syndrome can effectively relieve the clinical symptoms of patients with KOA， improve joint function， improve quality of life， reduce the contents of inflammatory factors IL-1<italic>β</italic> and TNF-<italic>α</italic> in serum， and increase the expression of TGF-<italic>β</italic>₁ level.