Plaunotol is an acyclic diterpene alcohol that was evaluated for anti-proliferative activity in four human cancer cell lines: HeLa; HT-29; MCF-7; and KB. After the cells were treated with plaunotol, cell viability was determined using the MTT assay. The results showed that plaunotol inhibited the growth of human cancer cell lines with an IC50 of 65.47±6.39 μM (HeLa), 72.92±5.73 μM (HT-29), 80.90±3.48 μM (KB), and 62.25±9.15 μM (MCF-7). For apoptotic detection, the cells treated with plaunotol were stained with Annexin-V/7-AAD reagent. The results indicated that plaunotol induced cell death or apoptosis. The transcription profile of apoptotic-associated genes, including TNF-α, BCL-2, BAX, and BAK genes, was determined using the qRT-PCR technique and the expression level was calculated as the relative quantitation (RQ). The ratio between RQ of BCL-2 and BAX suggested that plaunotol significantly induced apoptosis in HeLa, MCF-7, and HT-29 cell lines, in particular.