Ginsenoside Rk3 exerts the strong activity inhibiting NF-κB in a dose-dependent manner. HepG2 cells are pre-treated with different ginsenosides at concentrations ranging from 0.01 to 10 μM for 1 h, and induced with TNF-α for 20 h. Ginsenoside Rk3 significantly inhibits TNF-α-induced NF-κB transcriptional activity, with an IC50 of 14.24±1.30 μM. Ginsenoside Rk3 significantly inhibits TNF-α-induced NF-κB transcriptional activity, with an IC50 of 15.32±0.29 μM in SK-Hep1 cells, consistent with the data from HepG2 cells. Consistent with the inhibition of NF-κB, Ginsenoside Rk3 inhibits the induction of IL8, CXCL1, iNOS, and ICAM1 mRNA significantly in a dose-dependent manner.