Artemisia lavandulaefolia has been utilized in traditional medicines for the treatment of several diseases. In this study, we attempted to determine whether the essential oil and 1,8-cineole of A. lavandulaefolia induce apoptosis in KB cells. The oil and 1,8-cineole induced the cell death of KB cells as evidenced by the increased cell population in the sub-G1 phase, the appearance of condensed and/or fragmented nuclei, and the generation of a cleaved PARP product. The treatment of the cells with the oil also induced changes in the mitochondrial level of Bcl-2 and Bax, thereby inducing the release of cytochrome c into the cytosol. Furthermore, the oil increased the phosphorylation of extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase, and p38 MAPK, but 1,8-cineole activated pp38 and pJNK at the same concentrations. These findings show that the mitochondrial and MAPKs pathways might be involved in the oil-induced apoptosis, and may enhance our current understanding of the anticancer functions of the oil to a greater degree than 1,8-cineole.