Human microbiome studies have shown diversity to exist among different ethnic populations. However, studies pertaining to the microbial composition of CRC among the Indian population have not been well explored. We aimed to decipher the microbial signature in tumor tissues from North Indian CRC patients. Next-generation sequencing of tumor and adjacent tissue derived bacterial 16s rRNA V3-V4 hypevariable regions was performed to investigate the abundance of specific microbes. The expression profile analysis deciphered a decreased diversity among the tumor-associated microbial communities, and at the phyla level, Proteobacteria was differentially expressed in CRC tissues than adjacent normal. Further, DESeq2 normalization identified 4 out of 79 distinct species (pBacteroides massiliensis, Alistipes onderdonkii, Bifidobacterium pseudocatenulatum, and Corynebacterium appendicis. Thus, our findings suggest the use of these microbial signatures as putative biomarkers that can distinguish CRC tissues from their adjacent normal, which may shed light on the pathogenesis of CRC.