Climate change and resulting global warming are challenging environmental problems. Understanding the thermal adaptation mechanisms and survival strategies are of paramount importance. Fish has served as excellent animal model for understanding many biological processes. The present study was undertaken to investigate the proteomic changes in liver of murrel Channa striatus exposed to high temperature stress. Fishes were exposed to 36 °C for 4 days and liver proteome changes were analyzed using gel- based proteomics i.e. 2D gel electrophoresis, MALDI-TOF-MS and validation by transcript analysis. The study showed, besides others, up regulation of two sets of proteins, the antioxidant enzymes SOD, ferritin, GST and chaperones HSP60, PDI which was validated by transcript analysis. Further, gene expression analysis was also carried out in the fishes exposed to thermal stress for longer duration (30 days, in the laboratory and beyond, taking Channa collected from a hot spring runoff at a water temperature 36-38 °C); hsp60, sod and gst were found to continue to remain up regulated at 11, 8 and 3 folds, respectively in the hot spring runoff fish. Thus the study showed that SOD, GST and HSP60 play important role in thermal adaptation and survival under chronic heat stress.