Objective：To observe the protective effects of panax notoginseng saponins（PNS） on palmitic acid（PA） induced inflammation in HepG2 cells and to discuss the possible mechanism of PNS against inflammation. Methods：HepG2 cells were cultured in vitro. The control group，palmitic acid treatment group（PA group） and PNS treatment group were established according to the experimental requirements. The effects of PA and PNS on the proliferation of HepG2 cells were measured with MTT assay. Lipid accumulation was evaluated morphologically by oil red O staining. Real-time PCR was applied to determine the TNF-α mRNA expression. TNF-α in the cell-free culture supernatants was measured with highly specific enzyme-linked immunosorbent assay（ELISA） kits according to the manufacturer’s directions. Nuclear factor kappa B（NF-κB） activation was examined with immunofluorescence technique. Results：Palmitic acid treatment can induce apoptosis，lipidosis and inflammation in HepG2 cells while PNS pretreatment can suppress the TNF-α expression and releasing induced by PA. NF-κB activation induced by PA was also inhibited by PNS pretreatment. Conclusions：PNS has anti-inflammation effect on hepatocyte. The mechanism of PNS protective effect is partially due to the inhibition of NF-κB activation and TNF-α expression.