Photodynamic therapy (PDT) is a promising treatment for osteosarcoma, and pyropheophorbide‑α methyl ester (MPPa) is a second‑generation photosensitizer for tumor treatment. The present study aimed to determine the efficacy and possible mechanisms of MPPa‑PDT in the treatment of osteosarcoma MG‑63 cells. Flow cytometry and western blotting were used to detect cell cycle‑related indicators Cyclin D1, Cyclin E, Cyclin A and Cyclin B1. Cell migration and invasion abilities were detected using wound‑healing and Transwell chamber assays. Cellular endoplasmic reticulum stress (ERS), autophagy and apoptosis‑related indicators were detected by flow cytometry and western blotting. The results demonstrated that MPPa‑PDT blocked the MG‑63 cell cycle and inhibited cell migration and invasion. Additionally, MPPa‑PDT inhibited the activation of the Akt/mammalian target of rapamycin (mTOR) pathway. MG‑63 cells underwent ERS‑induced apoptosis following MPPa‑PDT treatment. Pretreatment with the mTOR phosphorylation inhibitor rapamycin affected the autophagy of MPPa‑PDT‑induced osteosarcoma MG‑63 cells and enhanced apoptosis through targeting mTOR.