A causal relationship between inflammation and cancer has long been suspected. It was demonstrated the presence of leukocytes in malignant tissues and claimed that tumors arise from regions of chronic inflammation. Hepatocellular carcinoma (HCC), the third leading cause of cancer mortality worldwide, commonly develops in the background of chronic hepatitis. The molecular and cellular mechanisms linking chronic inflammation to tumorigenesis remain largely unresolved. To investigate the roles of TNF-α on the formation and development of HCC, cell cycle, cyclin D1 and cyclin E was measured after treatment with TNF-α. Meanwhile, phosphorylated ERK1/2 and NF-κB activation were also assessed. After blocking the activation of ERK1/2 and NF-κB, the distribution of cell cycle and cyclin D1 expression was measured. It was found that G0/G1-to-S-phase transition was accelerated in human hepatic cell line L-02 treated by TNF-α treatment. Also TNF-α treatment can induce cyclin D1 expression in dose dependent but not cyclin E expression. Simultaneously, inhibition of NF-κB but not inhibition of ERK1/2 caused TNF-α-induced cell cycle arrest at G0/G1 and the increased levels of cyclin D1 expression. These result suggest that TNF-α promotes cell cycle progression by increasing expression of cyclin D1 due to NF-κB activation in human hepatic cell line L-02. Therefore, it enhances formation and progression of hepatocellular carcinoma. Suppression of a major signalling factor of inflammation, such as NF-κB or TNF-α, could thus be a tool to prolong the premalignant phase and inhibit tumour progression in chronic inflammatory diseases with high cancer risk.