Skeletal muscle accounts for ~40% of total body mass. The principle functions of skeletal muscle include supporting the body structure, controlling motor movements and storing energy. Rhabdomyosarcoma (RMS) is a skeletal muscle‑derived soft tissue tumor widely occurring in the pediatric population. In previous years, microRNAs (miRNAs) have been demonstrated to be important in skeletal muscle development, function and the pathogenesis of various diseases, including RMS. The present review provided an overview of current knowledge on the muscle‑specific and ubiquitously‑expressed miRNAs involved in skeletal muscle differentiation and their dysregulation in RMS. Additionally, the potential use and challenges of miRNAs as therapeutic targets in this soft‑tissue sarcoma were examined and the future prospects for miRNAs in muscle biology and muscle disorders were discussed.