MicroRNAs (miRNAs or miRs) are crucial for normal development and maintenance of homeostasis. Dysregulated miRNA expression contributes to numerous pathological conditions, including cancer tumorigenesis. However, a limited number of studies have examined the regulatory effects of miR-30a-3p in tumorigenesis. Therefore, the present study investigated the mechanistic process of tumorigenesis in liver cancer. The results revealed a high expression of DNA methyltransferase 3a (DNMT3a) and a low expression of miR-30a-3p in HepG2 cells compared with that in the L02 cell line. A luciferase reporter assay demonstrated that DNMT3a is a direct target of miR-30a-3p. In addition, DNMT3a overexpression significantly enhanced cell proliferation, which was reversed by a miR-30a-3p mimic Similarly, the miR-30a-3p mimic blocked DNMT3a-triggered cell cycle processes and apoptosis by attenuating active p-AKT and p-PI3K in HepG2 cells. In summary, the results of the present study demonstrate that miR-30a-3p is essential for cell proliferation regulation via its association with AKT/PI3K signaling in liver cancer. These results provide insight into the molecular mechanism by which miR-30a-3p inhibits liver cancer cell proliferation and provides a foundation for its clinical development and application.