ObjectiveTo explore the effect of hydroxyapatite nanoparticle (nHAP) on hepatocellular carcinoma (HCC) and its mechanisms. MethodsThe literatures about the effect of nHAP on HCC were reviewed and summarized. ResultsAs a new nanoparticle, nHAP could suppress the DNA synthesis and subsequent division and proliferation of HCC cells through the inhibition of proliferating cell nuclear antigen (PCNA) and telomerase gene expression and increase of intracellular Ca2+. Moreover, nHAP was able to suppress the differentiation and metastases of HCC cells through the effect on the expressions of Paxillin and P130cas and the decrease of expressions of multiple drug resistance gene protein, microvessel density, and vascular endothelial growth factor. Finally, nHAP induced the apoptosis of HCC tumor cells by the regulation of bcl-2 and bax protein expressions. The combined use of nHAP and chemoembolization drugs could enhance the efficacy, prolong drug duration and reduce toxicity. ConclusionnHAP can inhibit the division, proliferation, differentiation, and metastases, and promote the apoptosis of HCC cells and combined use with chemoembolization drugs can enhance the efficacy and reduce toxicity.