Objective To analyze the clinical effect of ultrasound-guided platelet-rich plasma combined with drug injection in the treatment of rotator cuff injury. Methods From December 2018 to April 2020, 100 patients with rotator cuff injuries admitted to our hospital were selected as the research object. According to the principle of random number table, the patients were divided into control group and observation group, 50 cases in each group. Patients in the control group were given ultrasound-guided drug injection therapy, and patients in the observation group were given ultrasound-guided platelet-rich plasma combined with drug injection therapy. Before treatment, after treatment and 1 month follow-up, visual analog (VAS) score was used to evaluate the degree of shoulder pain in the two groups. The active flexion range of motion (AFROM) and active abduction range of motion (AAROM) were compared between the two groups. The University of California at Los Angeles Scoring System (UCLA) was used to evaluate the effect of comprehensive treatment. At the same time, the adverse reactions were observed during treatment of two groups. Results After treatment and at one-month follow-up, the VAS scores of the two groups of patients were lower than before treatment, and the VAS scores of the observation group were lower than the control group, the differences were statistically significant (P <0.05). After treatment and during a month of follow-up, the AFROM angle and AAROM angle of the two groups of patients were higher than before treatment, and the above indexes of the observation group were higher than the control group, the differences were statistically significant (P <0.05). After treatment and at a month of follow-up, the UCLA ratings of the two groups of patients were better than before treatment, and the UCLA ratings of the observation group were better than the control group, the difference was statistically significant (P <0.05). No serious adverse reactions occurred during the treatment in both groups. Conclusion Ultrasound-guided platelet-rich plasma combined with drug injection for the treatment of rotator cuff injury has a good clinical effect, can significantly reduce patients "pain, improve patients" shoulder joint function, and has good safety.