Background: Medicinal plants, especially examples rich in polyphenolic compounds, have been suggested tobe chemopreventive on account of their antioxidative properties. Melissa officinalis L. (MO), an aromatic andmedicinal plant, is well known in thios context. However, toxicity against cancer cells has not been fully studied.Here, we investigated the selective anticancer effects of an MO extract (MOE) in different human cancer cells.Materials and Methods: a hydro-alcoholic extract of MO was prepared and total phenolic content (TPC) andtotal flavonoid content (TFC) were determined by colorimetric assays. Antioxidant activity was determined byDPPH radical scavenging activity. MTT assays were used to evaluate cytotoxicity of different doses of MOE (0, 5,20, 100, 250, 500, 1000 μg/ml) towards A549 (lung non small cell cancer cells), MCF-7 (breast adenocarcinoma),SKOV3 (ovarian cancer cells), and PC-3 (prostate adenocarcinoma) cells. Results: Significant (P<0.01) or verysignificant (P<0.0001) differences were observed in comparison to negative controls at all tested doses (5-1000μg/ml). In all cancer cells, MOE reduced the cell viability to values below 33%, even at the lowest doses. Inall cases, IC50 values were below 5μg/ml. The mean growth inhibition was 73.1%, 86.7%, 79.9% and 77.8% inSKOV3, MCF-7 and PC-3 and A549 cells, respectively. Conclusions: Our results indicate that a hydro-alcoholicextract of MO possess a high potency to inhibit proliferation of different tumor cells in a dose independentmanner, suggesting that an optimal biological dose is more important than a maximally tolerated one. Moreover,the antiprolifreative effect of MO seems to be tumor type specific, as hormone dependant cancers were moresensitive to antitumoral effects of MOE.