Nerve growth factor (NGF), a prototypical neurotrophic factor essential for neuronal cell proliferation and survival, has been implicated as a marker of tumor progression, as well as a potential target for novel therapeutic approaches in cancer. To investigate the functional potential of NGF in liver cancer in the present study, a stable NGF-overexpressing HepG2 cell line was generated. The scratch-wound assay was used to investigate cell motility and polarity. Western blotting was performed to evaluate the expression levels of epithelial-mesenchymal transition (EMT)-related proteins, including E-cadherin, N-cadherin and vimentin. Moreover, immunofluorescence was performed to investigate the arrangement of the actin cytoskeleton. Cell anoikis resistance was examined using a suspension culture model and cell apoptosis was examined via flow cytometry. The present results indicated that NGF overexpression in HepG2 cells disrupted HepG2 cell polarity and promoted cell motility. Furthermore, NGF overexpression induced EMT and actin cytoskeleton rearrangement in HepG2 cells, as well as enhanced anoikis resistance and prevented cellular apoptosis. Notably, a tropomyosin receptor kinase A receptor inhibitor blocked NGF-induced cell motility and apoptosis. Therefore, it was suggested that NGF serves a critical role in the invasion and metastasis of liver cancer. The use of NGF as a biomarker or potential new target could lead to the development of novel factors for diagnosis or for improving therapeutic strategies in liver cancer.