〔Abstract〕 Objective To investigate the effect of lysophosphatidic acid(LPA) on the expressions of CCAAT/enhancer binding protein β(C/EBPβ) and cyclooxygenase-2(COX-2) and proliferation in hepatocellular carcinoma cells, and further determine the possible effect of sinomenine hydrochloride(SIN), an anti-inflammatory drug, on it. Methods Human hepatocellular carcinoma Huh7 cell line was employed. The mRNA and protein expression levels of genes were detected by Real Time PCR and western blot, respectively. Cell proliferation was detected by MTT assay. Results After Huh7 cells were treated with 10 μmol/L of LPA for 0～6 h, the protein and mRNA expression levels of C/EBPβ and COX-2 were up-regulated in a time-dependent manner. After treatment with different concentrations of LPA(0～10 μmol/L) for 6 h, the protein and mRNA expression levels of C/EBPβ and COX-2 were increased in a concentration-dependent manner. SIN suppressed the increase of C/EBPβ and COX-2 and cell proliferation induced by LPA in a concentration-dependent manner. Conclusion LPA promotes the proliferation of human hepatocellular carcinoma Huh7 cells by inducing the expression levels of C/EBPβ-COX-2 pathway. SIN can inhibit LPA-induced cell proliferation through downregulating C/EBPβ-COX-2 pathway.