Iron oxide (Fe-O) has anti-tumor properties, due to its ability of catalyzing hydrogen peroxide (H2O2) of tumor cells to generate reactive oxygen species (ROS) and then cause ferroptosis. Its anti-tumor performance is restricted due to insufficient H2O2 in tumor cells. A nanomedicine, Au nanoparticles (NPs) grown on Fe-O, was integrated into poly-l-lactide (PLLA) scaffolds. Results indicated that Au NPs could consume glucose of tumor cells to produce H2O2, which supplemented reaction substrate. PLLA/Au@Fe-O scaffold showed enhanced anti-tumor activities against MG63, including increased mortality, decreased migration and colony formation. PLLA/Au@Fe-O scaffold promoted ferroptosis in MG63, including up-regulation of COX-2 protein, down-regulation of FTH1 protein and GPX4 protein. PLLA/Au@Fe-O scaffold also promoted autophagy in MG63, including down-regulation of P62 protein, and up-regulation of LC3BII/I. Mechanistically, PLLA/Au@Fe-O scaffold possessed enhanced anti-tumor activities through promoting ferroptosis and autophagy.