Mechanical pressure may contribute to the development of cancer; however, there is currently no evidence regarding the effect of mechanical pressure on liver cancer. In the present study, 2‑ and 3‑dimensional pressure‑loading systems were used to exert pressure on HepG2 and Huh‑7 cell lines. Cell proliferation and flow cytometry analyses were undertaken to observe the proliferative ability of pressure‑loaded cells. In addition, Transwell, wound‑healing and reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) assays were applied to evaluate the migratory and invasive ability of pressurized cells. Analyses of microRNA (miRNA) and mRNA expression profiles were performed to screen for differentially expressed miRNAs and mRNAs, which were validated by RT‑qPCR. Bioinformatics analyses were subsequently performed to investigate the putative target genes and associated pathways. The proliferation and invasion of HepG2 and Huh‑7 cell lines were significantly increased under a pressure of 15 mmHg for 24 h. Under this condition, five differentially expressed miRNAs (fold change ≥1.2, P≤0.05) and 10,150 differentially expressed mRNAs (fold change ≥2, P≤0.05) were identified. A total of 1,309 genes were identified from the integrative analysis of miRNAs and mRNAs. In addition, the bioinformatics analyses revealed that the majority of these miRNAs and mRNAs were associated with several pathways associated with cell proliferation and invasion, including 'PI3K/Akt signaling pathway', 'focal adhesion', 'integrin‑mediated signaling pathway', 'FOXO signaling pathway' and 'Hippo signaling pathway'. The present study described the pressure‑dependent proliferation and invasion of liver cancer cells, and revealed the potential molecular mechanisms underlying them. The identification of miRNAs and their putative targets may also result in novel treatment strategies for liver cancer.