Kahweol, the coffee-specific diterpene, has been reported to have anti-carcinogenic properties. Animal data support such a chemopreventive effect of coffee. However, the precise underlying protective mechanisms are poorly understood. In this study, the apoptotic effect of kahweol in human lung adenocarcinoma A549 cells was investigated. In cell viability assays and cell proliferation assays, kahweol exhibited anti-proliferative and pro-apoptotic effects on A549 cells in a time- and dose-dependent manner. Kahweol considerably inhibited the expression of Bcl-2 but increased that of Bax; it also stimulated the cleavage of caspase-3 and PARP (poly ADP-ribose polymerase). In addition, kahweol-induced apoptosis was confirmed by TUNEL assays. Furthermore, kahweol inhibited dose-dependent phosphorylation of signal transducer and activator of transcription 3 (STAT3). An overexpression in STAT3 led to resistance to kahweol-induced apoptosis, suggesting that STAT3 was a critical target of kahweol. These findings suggest that kahweol inhibited A549 cell growth and induced apoptosis via down-regulation of STAT3 signaling pathway.