Osteosarcoma (OS) is the most common type of primary malignant bone tumor and is characterized by complex genetic changes and resistance to conventional treatments. In this study, the role of miR-148a-3p in the progression and metastasis of OS was investigated. Firstly, it was found that the expression of miR-148a-3p was down-regulated in OS tissues and cell lines compared with that in adjacent non-neoplastic bone tissues and OS cell line. In addition, it was found that miR148a-3p inhibited cell proliferation, migration and invasion in MG-63 and U2OS cells and tumorigenicity in nude mice. Meanwhile, bioinformatic analysis suggested that phosphatidylinositol-4, 5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) gene is a potential target of miR-148a-3p. Then, it was found that PIK3CA can be directly regulated by miR-148a-3p via luciferase assay and western blot assay. Furthermore, PIK3CA knockdown induced effects on OS cell lines similar to those induced by miR-148a-3p. Taken together, these data suggest that miR-148a-3p suppresses cell proliferation, migration and invasion and PIK3CA was involved in miR-148a-3p associated biological functions in OS. Commonly down-regulated miR148a-3p may act as a tumor suppressor and a novel therapeutic strategy by downregulating PIK3CA expression.