The role of lipid metabolism played in cancer cell growth attracts more attention. SREBP1 is a common lipid regulatory factor. It has been reported that SREBP1 can promote tumor cell resistance. The aim of this study was to investigate its role in chemoresistance of colorectal cancer (CRC).,The expression of SREBP1 in CRC tissues was analyzed by immunohistochemistry. Using a viability assay, the sensitivity to 5-fluorouracil in two colon cancer cell lines (HT-29 and SW620) was measured and its correlation with different expression levels of SREBP1 protein by western blot was investigated.,The protein expression of SREBP1 in CRC tissues was higher than that in normal colon tissues. We found that over-expression of SREBP1 through SREBP1 gene transfection enhances the resistant of CRC cell lines to 5-FU, and SREBP1 silencing through SREBP1 shRNA transfection can promote apoptosis in 5-FU treated SW620 cells. Further study indicated that SREBP1 could inhibit the expression of caspase7 and reduce PARP1 cleavage fragments.,Our results suggest that SREBP1 protect the 5-FU treated CRC cells through caspase7 dependent PARP1 cleavage in apoptosis pathway and potentially provide a new target in the treatment of CRC.,IJCEP Copyright © 2019.