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Objective To investigate whether neutrophils extracellular traps (NETs) treated with microcystin-LR may promote the migration of colorectal cancer cell. Methods Isobaric tags for relative and absolute quantification (iTRAQ) technology was used to detect the secreted proteins in colorectal cancer cell culture supernatant after MC-LR exposure, and Gene Ontology (GO) functional enrichment analysis was performed to analyze in which pathway the differentially expressed proteins were enriched. The quantity of neutrophils in MC-LR-treated tumor tissue of xenograft nude mice was detected by flow cytometry. The expressions of CD11b, neutrophil elastase (NE) and citrulline histones 3 (citH3) in colorectal cancer tissues of BALB/c mice treated with MC-LR were detected by immunohistochemistry. The effect of NETs treated with MC-LR on colorectal cancer cell migration was determined by Transwell migration assay. Results Eleven differentially expressed proteins treated with MC-LR were screened out after MC-LR exposure(P＜0.05), and the differentially expressed proteins were enriched in the way of leukocyte migration. MC-LR increased the counting of neutrophils in colorectal cancer tissue of nude mice (P＜0.05). The expression of CD11b, NE and citH3 in orthotopic colorectal cancer tissues of BALB/c mice was increased after MC-LR administration compared with those in control group (P＜0.05). NETs treated with MC-LR enhanced the migration of colorectal cancer cell (P＜0.05). Conclusions MC-LR may promote migration of colorectal cancer cell by inducing the formation of NETs in the tumor microenvironment (TME).