Nuclear receptor binding protein 1 (NRBP1) is a ubiquitously expressed and highly conserved pseudokinase that has important roles in cellular homoeostasis. Despite recent advances in understanding the biology of NRBP1, the role of NRBP1 and its underlying mechanism in colorectal cancer (CRC) have not been fully elucidated. In the present study, we observed that NRBP1 expression levels were significantly reduced in CRC tissues compared with corresponding adjacent normal tissues, and high NRBP1 expression correlated with better prognosis in CRC. Overexpression of NRBP1 inhibited CRC cell proliferation and promoted apoptosis in vitro and in vivo. In contrast, knockdown of NRBP1 expression increased cell proliferation and decreased the percentage of apoptotic cells. Moreover, overexpression of NRBP1 activated caspase-dependent intrinsic apoptosis. In addition, we further discovered that NRBP1 regulated the apoptotic pathway through interaction with JNK. Finally, NRBP1 overexpression led to attenuated CRC growth in a xenograft mouse model. Our study illustrates the suppressor role of NRBP1 in CRC and provides a potential therapeutic target.