Objective To explore the effect of Sodium Hyaluronate combined with Compound Betamethasone Injection in the treatment of knee osteoarthritis. Methods A total of 84 patients with knee osteoarthritis admitted to the Department of Joint Surgery, the Second Affiliated Hospital of Inner Mongolia Medical University from January 2020 to December 2021 were retrospectively selected as the research subjects. According to medication regimen, they were divided into a reference group (42 cases) and a study group (42 cases). The reference group received Sodium Hyaluronate Injection. The study group was treated with Sodium Hyaluronate+Compound Betamethasone Injection. The efficacy,knee function, pain degree and disease symptom score were compared between the two groups. Results The total effective rate of the study group (95.24%) was higher than that of the control group (79.19%), hospital for special surgery(HSS) score after treatment was higher than that of the control group, the visual analogue scale (VAS) score was lower than that of the control group, joint pain, swelling, morning stiffness and other symptoms scores were lower than those of the control group, the differences were statistically significant (P＜0.05). Conclusion Sodium hyaluronate combined with Compound Betamethasone Injection in the treatment of knee osteoarthritis can improve the curative effect, relieve pain, and improve the disease symptoms and knee joint function.