Doxorubicin has a more potent cytotoxicity on both doxorubicin-sensitive osteosarcoma cells U-2OS and doxorubicin-resistant osteosarcoma cells U-2OS/DX30, U-2OS/DX100 and U-2OS/DX580 in the presence of H2S than that in the absence of H2S. The inhibitory effect of H2S on the P-glycoprotein in the doxorubicin-resistant osteosarcoma cells, resulting in the reduced efflux of doxorubicin and increased intracellular accumulation of DOXO, might be involved in the enhanced effectiveness of doxorubicin. This evidence concerns the gene ABCB1 and osteosarcoma.