This study was designed to explore the prognostic significance and functionality of STEAP2 (six-transmembrane epithelial antigen of prostate 2) in osteosarcomas and determine whether EFEMP2 (Epidermal growth factor-containing fibulin-like extracellular matrix protein 2) targets STEAP2 to facilitate osteosarcoma cell infiltration and migration. Here, EFEMP2 is linked to osteosarcoma.