Chemical investigation of the lichen Parmotrema praesorediosum (Nyl.) Hale led to isolate six phenolic compounds including praesorediosic (1), orcinol (2), orselinic acid (3), lecanorin (4), isolecanoric acid (5) and virensic acid (6). Among them, compound 1 appeared to be found for the first time in the nature. The structure of these compounds was elucidated by spectroscopic analyses of HRESIMS and NMR as well as the comparison of their NMR data with those in the literature. These compounds were evaluated for their cytotoxicity using sulforhodamine‐B assay against HeLa (human epithelial carcinoma), NCI‐H460 (human lung cancer), HepG2 (liver hepatocellular carcinoma) and MCF‐7 (human breast cancer) cell lines. Keywords. Lichen, Parmotrema praesorediosum, phenolic, praesorediosic, cytotoxic activity.