The present study provided the first compelling evidence that (i) NCOA5 is highly expressed in human CRC tissues; (ii) NCOA5 has a significant positive correlation with length of tumor, regional lymph node staging and cancer staging of CRC patients; and (iii) NCOA5 promotes proliferation, migration and invasion of CRC cells by upregulating Cyclin D1 and MMP9 as well as downregulating P27 through activating PI3K/AKT pathway. Here, NCOA5 is linked to colorectal carcinoma.