Overexpression of miR-139-5p increased drug sensitivity and suppressed the CD44+/CD133+ population in drug-resistant and CD44+/CD133+ cells by downregulating NOTCH1. In CRC samples and miR139-5p knockout mice, miR-139-5p expression inversely correlated with NOTCH1 expression. Here, NOTCH1 is linked to colorectal carcinoma.