Successful cancer treatment still requires new complexes or compounds from natural sources. Therefore, we investigated anti-growth/apoptotic effects of methanol extracts of the lichen species (Xanthoparmelia somloensis (Gleyn.) Hale, Usnea intermedia (A. Massal.) Jatta, Bryoria capillaris (Ach.) Brodo & D. Hawksw and Lobaria pulmonaria (L.) Hoffm.) on human lung (A549, H1299) and breast (MCF-7, MDA-MB-231) cancer cell lines. Anti-growth effects were monitored by the MTT and ATP viability assays. Cell death mode was evaluated by employing the fluorescence staining of nucleus, caspase-cleaved cytokeratin 18 detection, caspase 3/7 activity assay, Anneksin V cytofluorimetric assay and mitochondria membrane potential assay. Among the lichen extracts, Usnea intermedia exhibited strong anti-growth activity in a dose-dependent manner (1.56–100 µg/ml) compared to the others. Usnea intermedia was especially cytotoxic against MDA-MB-231 and H1299 cells (IC50 value for was found 3.0 and 10.2 μg/ml respectively). The cytotoxicity was resulted from apoptosis as proved by the presence of pyknotic nuclei, caspase 3/7 activity, phosphatidylserine translocation and loss of mitochondria membrane potential. In conclusion, Usnea intermedia warrants for further in vivo evaluation as a new alternative in cancer treatment.