Osteosarcoma，a kind of malignant bone tumor that often occurs in adolescents，has a strong metastatic capacity and poor prognosis. The occurrence of osteosarcoma and its resistance to cisplatin is known to be related to ERCC gene. As a key component of the nucleotide excision repair pathway, ERCC gene is found to regulate DNA repair. ERCC functional differences are mainly related to single nucleotide polymorphisms. The low expression may increase the risk of osteosarcoma, whereas the high expression may increase the resis- tance to cisplatin. In addition, ERCC gene is related to occurrence and prognosis of osteosarcoma, and is of great significance to the chemo- therapy drugs selection. The targeted inhibition of ERCC provides possibility to reduce the resistance of cisplatin. Our review highlights the research progress of ERCC in osteosarcoma and provides relevant concepts for further clinical translational applications.