Objective To determine the analgesic efficacy of ultrasound-guided corticosteroid mixture injection in the treatment of senile osteoarthritis of the knee. Methods A total of 31 patients (35 knees) with senile osteoarthritis of the knee treated with ultrasound-guided corticosteroid mixture injection in our hospital from May to December 2015 were recruited in this study. Corticosteroid mixture was made using triamcinolone acetonide, 2% lidocaine and water for injection with the volume ratio of 2∶1∶1. Visual analog scale (VAS) was used to evaluate the patients preoperatively, and in 4 weeks and 6 months postoperatively. The satisfaction degree of the patients was investigated 6 months postoperatively. Results The one-time successful rate of the procedure was 100%. Compared with the VAS score preoperatively (5.2±1.5), the score was significantly reduced in 4 weeks (0.5±0.7) and 6 months postoperatively (1.0±1.2, both P<0.05). But, no obvious difference was found in the score between the 2 postoperative time points (P>0.05). The pain disappeared or significantly relieved in 33 knees (94.2%) in 6 months after treatment, with a satisfaction rate of 91.4%. Conclusion With ultrasound precise positioning and real-time guidance, local injection of corticosteroid mixture shows good anti-inflammatory analgesic effect in the treatment of senile osteoarthritis of the knee, and it is worth of recommending.