Background and Aims Studies have shown that a variety of microRNAs (miRNAs) may play crucial roles in the occurrence and development of liver cancer, and their action mechanisms still need to be studied and determined. Therefore, this study was conducted to further screen and validate the key miRNAs from the differentially-expressed miRNAs that have been reported in liver cancer, and then investigate their action mechanisms.Methods The common differentially-expressed miRNAs in liver cancer tissue and serum/plasm of liver cancer patients versus normal liver tissue and serum/plasm of healthy subjects were screened from the published studies. The expressions of goal miRNAs in normal liver cells and liver cancer cells were verified by qRT-PCR method. Using overexpression and inhibition strategies, the influences of goal miRNAs on invasion ability (Transwell invasion assay) and proliferation capacity (MTT assay) of liver cancer cells were observed, and also the expressions of goal miRNAs in 30 samples of clinical specimens were detected and their impacts on survival of liver cancer patients were analyzed through KM plotter website. The target genes of goal miRNAs were predicted and analyzed using miRDB and GEPIA databases and were further validated by reverse experiment and dual-luciferase reporter assay.Results There were 4 common up-regulated miRNAs (miR-18a-3p, miR-221-3p, miR-222-3p, miR-224-3p) and 2 down-regulated miRNAs (miR-26a-3p, miR-125b-3p) in liver cancer tissue (vs. normal liver tissue) and serum/plasma of liver cancer patients (vs. serum/plasma of healthy individuals). The qRT-PCR experiment confirmed that miR-18a was highly expressed and miR-26a was weakly expressed in liver cancer cells compared with normal liver cells (both P<0.05). Overexpression/inhibition of miR-18a expression promoted/reduced the invasion and proliferation capacities of liver cancer cells (all P<0.05), while overexpression/inhibition of miR-26a exerted confused influences on the invasion abilities and proliferation capacities of liver cancer cells. The results of analysis showed that ADCY1 was target gene of miR-18a-3p, overexpression of ADCY1 partially reversed the above actions of miR-18a-3p on liver cancer cells, and meanwhile, the up-regulated miR-18a-3p can inhibited the expression of ADCY1 by binding to the ADCY1 mRNA 3'UTR.Conclusion MiR-18a-3p may play a critical role in the occurrence and development of liver cancer. Its expression is up-regulated in liver cancer cells and tissues, which can promote the invasion and proliferation capacities of liver cancer cells by inhibiting the expression of downstream target gene ADCY1.