Objective: To investigate the clinical effects of acupuncture under bone ultrasound in the treatment of knee osteoarthritis and the effects on patients’ joint soft tissues. Methods: A total of 106 patients with GO admitted to our hospital from February 2021 to June 2022 were randomized into a research group and a control group (n=53). The research group was given musculoskeletal ultrasound under acupuncture and the control group was given conventional ultrasound-guided acupuncture. The visual analog scale (VAS) and knee function assessment (Lysholm) were used to assess patients’ pain and knee function before and after treatment, and to observe the ultrasound images of the knee joint, and to record the changes of knee circumference, joint fluid area, synovial thickness, and other indexes. In addition, patients were counted for adverse reactions during treatment. After discharge, a 3-month follow-up was performed to assess the quality of life of patients in both groups after treatment using the Simplified 36 Health Survey Scale (SF-36). Results: After treatment, VAS and Lysholm scores decreased in both groups, and were lower in the research group than in the control group (P<0.05). Before and after treatment, the circumference of the knee joint, joint fluid area and synovial thickness did not change dramatically in the research group (P>0.05), all of which were higher than those in the control group (P<0.05). In addition, the incidence of adverse reactions was lower in the research group than in the control group (P<0.05). The follow-up results revealed that the research group had higher scores in the areas of physical function (PF), role physical (RP), bodily pain (BP), general health (GH), and social function (SF) than the control group (P<0.05). Conclusion: The clinical effect of GO treatment with musculoskeletal ultrasound under needle knife is remarkable. It can effectively reduce the pain condition of patients and improve the function of the knee joint, while causing less damage to the joint soft tissues, with high safety. Thus, it is worth promoting.