To evaluate the anti-proliferative effect of kappa-selenocarrageenan (KSC) in combination with paclitaxel (Taxol) on human hepatoma cell line HepG2 and their synergistic effect. The cytotoxic effect of drugs on HepG2 cells was measured by MTT assay, and the King’s principle was used to evaluate the interaction of drug combination. Cell cycle and apoptotic rate were detected by flow cytometry (FCM). Expression of cyclin A, chk2, Cdc25A and cdk2 were detected by flow cytometry and western blotting. KSC and Taxol demonstrated growth inhibitory effect on HepG2 cells in a dose-dependent manner, with the IC50 values of Taxol decreased dramatically from 1.684 nmol/L to 0.272 nmol/L while combining with 30 mg/L KSC (P<0.01). In addition, additive activity was observed when 30 mg/L KSC was combined with Taxol (0.5~5 nmol/L) (q=0.85~1.15). FCM results showed that KSC and Taxol both blocked cell cycle in S phase and their combination enhanced S phase arrest. Western blotting analysis revealed that Cyclin A and chk2 protein expression in HepG2 cells increased but Cdc25A and cdk2 expression decreased.