Objective To perform a genome-wide histone modification profiling of Tibet minipigs and to comparewith the differences in histone modifications in different tissues. Methods Tissue samples of blood, liver, ileum, andmuscle of two three-month-old male Tibet minipigs were collected and used for chromatin immunoprecipitation sequencing.Through quality control, raw data were filtered and compared with the reference genome, then we used MACS software toenrich clean reads in the genome. Results The enrichment positions of different histone modifications differed in the genepromoter region, and the distribution patterns were roughly divided into two types. One type, H3K4me3, was mainlydistributed on both sides near the transcription start site, exhibiting a peak with a narrow range at the downstream position.The second type, H3K9me3, was distributed more evenly throughout the gene promoter, exhibiting a broad peak shape witha low middle and two high sides. Genes affected by the tissue-specific histone modifications differed, and the correspondingfunctional pathways were relatively extensive, but they were all involved in the transcriptional regulation of the RNApolymerase II promoter. Conclusions Our study provides a dataset of histone modification annotations for four types ofdifferent tissues of Tibet minipigs, which will serve as a foundation for future studies using transcriptional regulation of the Tibet minipig as a biomedical animal model.