Knee osteoarthritis (KOA) is a common degenerative joint disease and immune system dysregulation has been implicated in its pathogenesis. The effect of arthroscopic knee surgery, an important method for KOA diagnosis and treatment, on the expression of immune regulators remains poorly understood. We aimed to investigate the clinical efficacy of such surgery and its impact on IL-1β, CXCL13, and TNF-α expression in the knee joint synovial fluid of osteoarthritis patients. Fifty-seven patients having undergone arthroscopic knee surgery in our hospital were included. Visual analog scale (VAS) and Lysholm scores were recorded before surgery, and knee joint synovial fluid was collected during the procedure. According to Outerbridge cartilage damage score (grade 0, 1, 2, 3, or 4), patients were divided into five groups. In addition, VAS and Lysholm scores were recorded and knee joint synovial fluid was collected after a six-month follow-up period. Expression of IL-1β, CXCL13, and TNF-α in synovial fluid samples was then measured. In each group, levels of these molecules and VAS and Lysholm scores were significantly lower after surgery (P < 0.05). IL-1β, CXCL13, and TNF-α levels were significantly elevated in patients with higher cartilage damage scores compared to those with lower scores. Arthroscopic knee surgery can reduce IL-1β, CXCL13, and TNF-α levels in the knee joint synovial fluid of osteoarthritis patients. Moreover, reduced presence of these molecules correlates with clinical improvement of this condition. Therefore, reduction in IL-1β, CXCL13, and TNF-α expression might be used as a factor for long-term osteoarthritis prognosis.