Chromatin immunoprecipitation coupled with next-generation sequencing (ChIP-seq) is a crucial method for examining transcription factor binding and histone modifications across the entire genome. This is a key step in deciphering the complex mechanisms that control cancer immunosurveillance. Here, we provide a comprehensive protocol covering all the steps needed to obtain DNA for ChIP-seq library preparation, starting from tissue dissection, followed by fixation, chromatin preparation, immunoprecipitation, and finally DNA purification. The protocol is optimized for frozen mice tissues, but can be easily adapted for use with any model organism. The resulting immunoprecipitated chromatin is suitable for library preparation and sequencing on an Illumina platform.