Background. Hepatocellular carcinoma (HCC) is a significant cause of human death in the world. Recently, it is found that midazolam can modulate miRs to participate in HCC progression. This research project was designed to elucidate the impacts of midazolam and miR-217 on HCC cell metastasis and apoptosis. Methods. Human HCC cell strains (Hep3B and SK-HEP-1) were selected and intervened by midazolam at different concentrations in our research. miR-217-inhibitor intervened in the two HCC cell strains to observe the alterations of cell migration, invasiveness, and apoptosis. The miR-217 level in HCC cells was identified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Results. As midazolam concentration was elevated, Hep3B and SK-HEP-1 viabilities were more obviously suppressed. The 10 mu g/mL concentration was selected for analysis since Hep3B and SK-HEP-1 had an IC50 of 10.57 mu g/mL and 9.35 mu g/m, respectively. The qRT-PCR results showed the decreased of miR-217 in HCC cells, which was enhanced notably by midazolam intervention. Compared with the blank group, the invasiveness and migration (Transwell assay) of miR-217-inhibitor-transfected HCC cells were distinctly enhanced and the apoptosis rate (flow cytometry) was noticeably reduced. Conclusion. Midazolam can upregulate miR-217 in HCC cells, thus inhibiting HCC cell metastasis and apoptosis.