Our results reveal that SeNPs@Am can inhibit human hepatocellular carcinoma multi-biobehaviors even in low concentration through activation of the P53/P73/P21/P27 signaling with inhibition of CDK-2 and ICBP90, and the caspase signaling, indicating that it may be a promising drug for hepatocellular carcinoma. This evidence concerns the gene TP53 and hepatocellular carcinoma.