Sertraline exerted effective anticancer activity in colorectal cancer cells and sertraline synergistically enhanced the efficacy of the chemotherapeutic agent paclitaxel against colorectal cancerSertraline augmented paclitaxel‐induced autophagy by increasing autophagosome formation indicated by elevated LC3‐II/I ratio and promoting autophagic flux by degrading autophagy cargo receptor SQSTM1/p62. This evidence concerns the gene SQSTM1 and colorectal cancer.