Objective This study is aimed at exploring the influence of circular RNA- (circRNA-) RANGAP1 targeting microRNA- (miR-) 542-3p/myosin regulatory light chain interacting protein (MYLIP) on the biological function of osteosarcoma (OS) cells. Methods Tumor tissues and normal tissues were collected from OS patients and circ-RANGAP1, miR-542-3p, and MYLIP expression was tested by RT-qPCR. The correlation between the clinicopathology/prognosis of patients with OS and circ-RANGAP1 expression was observed. Human OS cell line MG-63 was screened to determine the influences of circ-RANGAP1 and miR-542-3p on OS cell progression. The targeting relation of circ-RANGAP1, miR-542-3p, and MYLIP was probed. Results circ-RANGAP1 expression was elevated in tumor tissues from OS patients, which was correlated to the poor clinicopathology. circ-RANGAP1 expression was augmented in males or patients younger than 20 years old or patients with advanced OS. Higher circ-RANGAP1 expression indicated a poor prognosis in OS patients. After silencing circ-RANGAP1 or elevating miR-542-3p in MG63 cells, cell progression was limited. miR-542-3p downregulation reduced the therapeutic efficacy of silenced circ-RANGAP1. circ-RANGAP1 bound with miR-542-3p to target MYLIP. Conclusion Silenced circ-RANGAP1 boosts MYLIP expression via competitive binding of miR-542-3p to facilitate OS cell progression.