This work aims to determine the response of Hypogymnia physodes (L.) Nyl. (hooded tube lichen) collected in an unpolluted site (Yenice Forest in Karabük, Turkey) to stress conditions. In the present study, the effect of exposure to different heavy metals (Cd+2, Pb+2, and Cr+6) for different durations and UV radiations dosages on lichen was examined at the physiological and molecular levels. The effects of stress conditions were determined in the case of different parameters concerning heavy metal, protein, chlorophyll, and carotenoid contents and changes in the DNA profiles. According to the results obtained that exposure to heavy metals and UV radiations leads to a physiological response in a concentration and dose-dependent manner through differences in chlorophyll, protein content in heavy metals and UV treated lichen specimen. Furthermore, changes in RAPD assay and DNA methylation analysis showed that homologous nucleotide sequences in the genome from untreated and stress conditions treated lichen specimen showed different band patterns and methylation under heavy metals and UV stress. The results determined that lichen specimen suggest as a possible bioindicator able to measure the biological effects of heavy metal pollution and damage to UV radiation.