This study aimed to identify genomic regions involved in animal responses to chronic and acute Heat challenges in 1149 pigs tested in three climatic environments (temperate, tropical, and temperate Heated to 30 °C for 3 weeks). Production (growth rate, feed intake and efficiency, backfat thicknesses) and thermoregulation (rectal and cutaneous temperatures) traits were recorded in a backcross between Large White and Créole pigs. Genome-wide association studies were applied to the full population assuming SNP effects to be the same in both environments or to depend on the environment (GxE), and to the population in each environment separately. The genetic models used linkage disequilibrium in all chromosomes (LD) or only in Large White chromosomes (LW), or breed-of-origin of F1 alleles through linkage analyses (LA). Results Fifty-two regions distributed on 16 autosomes were detected. Most were identified with the LW or LD analyses, indicating both a large variability of effects in Large White in response to Heat stress, and high variability among the 10 Créole genomes segregating in the design. However, for thermoregulation traits, the majority of QTLs were detected with the LW model, suggesting interesting segregation of susceptibility and resistance alleles within the Large White breed. Ten regions were detected with the GxE model, mainly corresponding to significant effects in the temperate environment and no effect in the tropical situation, except for two regions on chromosome 2, which affected backfat thickness and growth rate, respectively. Twenty-four regions were detected for thermoregulation traits, but none were significant for both rectal and cutaneous temperatures. Of the 13 QTL regions detected for traits recorded during acute stress, four were also detected for similar traits during chronic stress, suggesting some consistency of responses during both stresses, although nine QTL regions were only detected during acute heat stress. Conclusions Measuring direct indicators of responses to heat stress, such as thermoregulatory responses, is essential to detect QTL and propose candidate genes involved in these responses. Multiple QTL for thermoregulatory responses segregate in the Large White breed were detected, paving the way for opportunities to select for heat stress resilience in European pig breeds.