Our present study has revealed the following novel findings: (i) exogenously overexpressed miR-875-5p suppresses tumor regeneration in 6 CRC xenograft models and suppresses cell growth in vitro and in vivo; (ii) miR-875-5p overexpression inhibits CRC cells metastasis; (iii) inhibition of miR-875-5p in CRC cells results in high clonal clonogenic, and tumorigenic properties; (iv) miR-875-5p overexpression promotes CRC cells apoptosis, and inhibition of miR-875-5p inhibits CRC cell apoptosis; (v) miR-875-5p targets EGFR in CRC cells and negatively expressed with EGFR. Here, EGFR is linked to colorectal carcinoma.