Objective To explore the application value of Tongluo Qutong ointment combined with ultrasound-guided pulsed radio frequency therapy in the treatment of knee osteoarthritis (KOA) patients. Methods Fifty-nine KOA patients treated with Tongluo Qutong ointment combined with ultrasound-guided pulsed radiofrequency therapy from March 2021 to March 2024 in our hospital were selected as the observation group, and fifty-nine KOA patients treated with ultrasound-guided pulsed radiofrequency therapy during the same period were selected as the control group. The efficacy of the two groups, pain scores before and after treatment, KOA severity index (ISOA) scores, knee joint function, serum inflammatory factor levels, and quality of life were compared. Results The total effective rate of the observation group (96.61%) was higher than that of the control group (84.21%) (P<0.05). The visual analog scale (VAS) and ISOA scores for pain in the observation group were lower than those in the control group after treatment (P<0.05). The functional score of the knee joint in the observation group after treatment was higher than that in the control group, and the WOMAC score was lower than that in the control group (P<0.05). After treatment, the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hs-CRP) in the observation group were lower than those in the control group (P<0.05). Additionally, the scores for each item in the World Health Organization Quality of Life Assessment Brief Scale (WHOQOL-BREF) in the observation group were higher than those in the control group after treatment (P<0.05). Conclusion The use of Tongluo Qutong Ointment as an adjunct to pulsed radiofrequency therapy in patients with KOA can effectively alleviate pain, delay disease progression, inhibit inflammatory responses, improve knee joint function, and enhance treatment efficacy and quality of life prognosis.