Mexican Coreño Creole cattle are an important genetic resource adapted to local environmental conditions, so the study of their genetic diversity is essential to know their status and implement conservation programs and their use for crossbreeding. This study evaluated the genetic diversity of heat stress tolerance characteristics of Coreño Creole cattle, and a gene ontology enrichment was performed to know the biological processes in which candidate genes are involved. A total of 48 samples from three localities of Nayarit were genotyped using 777 K Illumina BovineHD BeadChip and 34 single nucleotide polymorphisms associated with candidate genes were selected. Genetic diversity was analyzed using allelic frequencies, expected heterozygosity (He), and Wright's fixation index (FST) using PLINK v1.9 software. Candidate genes were uploaded to the open-source GOnet for pathway analysis and linkage to biological processes. Coreño Creole cattle showed low genetic diversity (He = 0.35), the average FST obtained was 0.044, and only eight markers had allele frequencies higher than 0.80 in the three locations. We found that the genes GOT1 and NCAD are related in the biological processes of stress response, cell differentiation, and homeostatic process. The results revealed that Coreño Creole cattle have low genetic diversity; this could be due to the isolation of these populations., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)