The effects of six lipophilic vitamins: tretinoin (ATRA), vitamin D₃ (VD₃), VE, VK₁, VK₃, and VK₅ on cell proliferation and apoptosis in human A375 melanoma cells were investigated. VD₃, VK₃, and VK₅ were found to inhibit cell proliferation significantly at concentration ranges of 10—100 μmol/L (p<0.01), while the other vitamins did not show inhibitory effects at 100 μmol/L. VK₃ and VK₅ showed the strongest effects with IC₅₀ values of less than 10 μmol/L. Dacarbazine slightly inhibited the proliferation of A375 cells at a concentration range of 25—100 μmol/L, but the effects were not statistically significant. VK₃ and VK₅ increased annexin-V positive apoptotic cells, as well as activating caspase-3, in A375 cells. Our findings showed that VD₃, VK_3, and VK₅ inhibited the growth of dacarbazine resistant human melanoma cells, while ATRA, VE, and VK₁ had little effect on the cell growth. The effects of VK₃ and VK₅ were observed at concentrations lower than 10 μmol/L, which are suggested to have resulted from apoptosis-induction in the melanoma cells.