Essential oils, with plant origin, have been of special attention in cancer research during recent years. Despite many reports on cytotoxic effects of plants from genus salvia, the potential application of their extracts in cancer therapy remains to be assessed in more precise and detailed examinations on the main cause of such effects. In this research, the cytotoxic effect and anticancer activity of essential oils from S. leriifolia on human Transitional Cell Carcinomaa (TCC) were studied in vitro. The antiproliferative activity of essential oils on TCC and L929 (control) cells was determined by 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide (MTT) assay, by which the mitochondrial dehydrogenase enzyme activity is assessed based on reduction of the MTT to purple. The amount of essential oils to induce 50% of cells to die, designated as IC50, was determined by repeated experiments and application of different doses of the essence. The established IC50 on TCC cells for the essences extracted in two different years of 2006 and 2008 and from two locations of Bajestan and Neyshabour was respectively as: 466 and 250 μg/ml, and 233 and 212 μg/ml. S. leriifolia essential oil did not show any detectable effect on L929 cells in this range of concentration. S. leriifolia essential oil has inhibitory effects on the growth of both TCC and normal L929 cell lines, although the effective concentrations were significantly different in these cell lines. This effect was dose dependent.