Colorectal cancer (CRC) is one of the most common cancers in the world. Although genomic mutations and SNPs have been extensively studied, the epigenomic status in CRC patient tissues remains elusive. Here, we profiled active enhancers genome-widely in paired CRC patient tissues through H3K27ac ChIP-Seq, together with genomic and transcriptomic analysis. Totally we sequenced 73 pairs of CRC tissues and generated 147 H3K27ac ChIP-Seq, 144 RNA-Seq, 147 whole genome sequencing and 86 H3K4me3 ChIP-Seq files. Our analysis discovered 5590 gain variant enhancer loci (VEL) and 1100 lost VELs in CRC, and 334 gain variant super enhancer loci (VSEL) and 121 lost VSELs. Multiple key transcription factors in CRC were predicted with motif analysis and core regulatory circuitry analysis. Further experiments verified the functions of 6 super enhancers governing PHF19, LIF, SLC7A5, CYP2S1, RNF43 and TBC1D16 in regulating cancer cell migration, and we identified KLF3 as a novel oncogenic transcription factor in CRC. Taken together, our work provides important epigenomic resource and novel functional factors for epigenetic studies in CRC.