Two series of amino-modified derivatives of (S)-perillyl alcohol were designed and synthesized using (S)-perillaldehyde as the starting material. These derivatives showed increased antiproliferative activity in human lung cancer A549 cells, human melanoma A375-S2 cells and human fibrosarcoma HT-1080 cells comparing with that of (S)-perillyl alcohol. Among these derivatives, compounds VI5 and VI7 were the most potent agents, with the IC50s below 100 μM. It was demonstrated that the antiproliferative effect of VI5 was mediated through the induction of apoptosis in A549 cells.