Osteosarcoma (OS) is the most common type of bone cancer. Even with early diagnosis and aggressive treatment, the prognosis for OS is poor. In the present study, we investigated the proliferation and invasion inhibitory effect of apigenin on human OS cells and the possible molecular mechanisms involved. The cell viability of U2OS and MG63 human OS cell lines was detected by MTT assay. Cell cycle progression and invasion were assessed by flow cytometry and the Matrigel Boyden chamber assay, respectively, and the involvement of molecular mechanisms was examined by western blot analysis. We demonstrated that apigenin inhibited proliferation and reduced invasion in human OS cells, and downregulated the expression of beta-catenin in OS cells. Furthermore, the inhibitory effect of apigenin on OS cells was reversed by overexpression of beta-catenin, but enhanced by knockdown of beta-catenin. Collectively, our results showed that apigenin inhibits the tumor growth of OS cells by inactivating Wnt/beta-catenin signaling. Therefore, apigenin is a promising chemotherapeutic agent that may be used in the treatment of human OS.