Objective: To explore the efficacy of electroacupuncture combined with comprehensive rehabilitation in the treatment of knee osteoarthritis (KOA) and its influence on pain, joint function, and the level of transforming growth factor-β1 (TGF-β1) in joint fluid. Methods: A total of 110 KOA patients admitted to our hospital from January 2020 to March 2021 were selected and divided into a control group (n=58) and an observation group (n=52) according to different intervention methods. The control group was treated with comprehensive rehabilitation, and the observation group was treated with electroacupuncture on the basis of the control group. The clinical efficacy and TCM syndrome score, pain [Visual Analogue Scale (VAS)], joint function [Lysholm Knee Score Scale (LKSS), joint fluid TGF-β1 and inflammatory factors interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α)] levels were compared between the 2 groups. Results: The total effective rate of the observation group was significantly higher than that of the control group (90.38% vs 75.86%, P<0.05). The TCM syndrome score in the observation group after treatment was significantly lower than that in the control group (P<0.05). Compared with the control group, the VAS scores at 14 d, 30 d and follow-up in the observation group were lower, and the LKSS scores were higher (P<0.05). After treatment, the levels of TGF-β1 in the synovial fluid of the observation group were higher than those of the control group, while the levels of IL-6 and TNF-α were lower (P<0.05). Conclusion: Electroacupuncture combined with comprehensive rehabilitation has a significant effect on KOA, which can significantly improve the clinical symptoms of patients, relieve pain, enhance joint function, increase TGF-β1 level and inhibit inflammatory response may be its mechanism.