【Abstract】 Objective To study the role of ADAM17 in the proliferation of liver cancer HepG2 cells, and its underlying mechanism. Methods ShRNAADAM17 was used to abrogate the expression of ADAM17 in liver cancer HepG2 cells. In this study, HepG2 cells were divided into the control group, the shRNAscrambled group (negative group) and the shRNAADAM17 group. At different time points (0h, 24h, and 48h), the cell viabilities of HepG2 cells were analyzed by MTT assay. After 4h of interventions, the mRNA expression of ADAM17, NOTCH1, and Hes1 was measured by qPCR. Then, after 4h of interventions, western blot was performed to identify ADAM17, NOTCH1, and Hes1 protein expression. Results The cell viabilities of liver cancer HepG2 cells were timedependently inhibited by shRNAADAM17. However, no differences in the cell viabilities of liver cancer HepG2 cells between the control group and the shRNAscrambled group was found. The mRNA and protein expression of ADAM17, NOTCH1, and Hes1 were all reduced by shRNAADAM17 in liver cancer HepG2 cells, after 4h of interventions. There was no difference in ADAM17, NOTCH1, and Hes1 expression between the control group and shRNAscrambled group. Conclusion In the current study, our results indicate that the proliferation of liver cancer HepG2 cells could be suppressed by the downregulation of ADAM17 possibly through inhibition of NOTCH1/Hes1 signaling pathway, suggesting ADAM17 as a potential treatment target of liver cancer in future.