Colorectal cancer (CRC) is a general cancer worldwide. Increasing evidences showed that Sevoflurane (Sev) and microRNA-944 (miR-944) contributed to CRC pathogenesis, but the molecular mechanism is still larger unknown. Thereby, the study was devoted to investigate the functions and mechanisms of Sev and miR-944 in CRC progression. Level of miR-944 was distinctly suppressed, while ROBOR1 expression was apparently induced in CRC tissues and cell lines. The effects of Sev on promoting HCT116 and SW480 cells apoptosis, impeding migration and invasion were aggravated by miR-944 mimic; these effects of Sev were rescued by miR-944 inhibitor yet. Meanwhile, ROBO1 as a target of miR-944, its silencing reverted miR-944 inhibitor effects on cell behaviors of cell apoptosis, migration and invasion in vitro. Sev modified cell behaviors, such as apoptosis, migration, and migration via miR-944/ROBO1 axis in CRC cells, and may supply a novel therapeutic insight for clinical CRC.