Assessing the adaptability of slow-growing rural chickens for improving thermotolerance to suit the global climate change is a major research need. This work was aimed to evaluate the adaptability of CARI-Debendra chickens and to identify the polymorphism as well as expression profiling of thermotolerant genes (HSP70 and GRP78) under prevailing temperature-humidity indices and thermal stress in a coastal environment. One hundred sixty straight run chicks were reared at THI≥75 (control) and THI>80 under coastal climate till 12 weeks. Polymorphism of HSP70 and GRP78 candidate genes were explored using restriction enzymes TaqI and HaeIII to identify possible thermotolerance markers. Expression profiling of both the genes in liver, intestine and pectoralis muscle was determined through quantitative real-time PCR. Rectal and body surface temperature recorded in the neck and back showed significant differences (P < 0.01) with higher temperature in THI>80 group. Comparatively lower live weights (P < 0.05) and poor FCR were recorded in THI>80 group. The villi height in all intestinal segments was significantly lower (P < 0.01), but deeper crypt depth was observed in THI>80 than control group. A lowest thymus weight (P < 0.05) was noted with no significant differences in immune response in treatment group. Serum levels of cholesterol, activities of lactate dehydrogenase, creatinine kinase and concentration of potassium, sodium and thyroxine hormone were not different between the 2 groups. The concentration of triiodothyronine and chloride ion was lower in THI>80 group indicating adaptive changes for thermoregulation. HSP70 gene expressions in the three tissues were differentially increased (P < 0.01) by temperature-humidity indices, but the expression of GRP78 was not different between the 2 groups. The results concluded that the environmental factors interact with genetics on adaptability towards thermotolerance in slow-growing chickens.