Objective To investigate the clinical effect of spleen-tonifying and kidney-nourishing prescription in the prevention and treatment of aromatase inhibitor-induced arthralgia. Methods A total of 81 postmenopausal patients with early-stage hormone receptor-positive breast cancer who underwent endocrine therapy with aromatase inhibitors from October 2017 to September 2018 were enrolled and randomly divided into treatment group with 41 patients and control group with 40 patients based on the method of simple randomization and parallel control. The patients in the control group were given conventional calcium+vitamin D treatment, and those in the treatment group were given oral administration of the spleen-tonifying and kidney-nourishing prescription in addition to the treatment in the control group. The two groups were compared in terms of bone mineral density (BMD), Brief Pain Inventory-Short Form (BPI-SF) score, and Morisky Medication Adherence Scale-8 (MMAS-8) score before and after treatment. All patients were observed for 6 months. Results Compared with the control group, the treatment group had significantly greater increases in BMD of the lumbar vertebra and the femoral neck after treatment (P<0.05). Compared with the control group, the treatment group had a significantly greater reduction in the most severe pain score of BPI-SF (P<0.05). At the end of months 3, 4, 5, and 6 of treatment, the treatment group had a significantly higher MMAS-8 score than the control group (P<0.05). Conclusion Spleen-tonifying and kidney-nourishing prescription has a satisfying clinical effect in the prevention and treatment of aromatase inhibitor-induced arthralgia and can alleviate arthralgia and improve compliance with endocrine therapy in patients with breast cancer.