Accumulating evidence showed that cytokines are involved in the development of cancer. IL-13 was showed to induce epithelial-mesenchymal transition and promote metastasis in colorectal cancer, providing a promising therapeutic target for cancer patients. Interestingly, recent studies showed that propofol, one of most common intravenous anesthetic agent, may have antitumor function in different cancer type. However, the impact of propofol on colorectal cancer and IL-13 induced epithelial-mesenchymal transition remains unknown. Herein, we found that propofol can effectively suppress cell proliferation in colorectal cell lines RKO and SW480 cells by using MTT assay. Furthermore, wound healing assay and migration assay demonstrated that propofol has the ability to inhibit epithelial-mesenchymal transition that induced by IL-13 in RKO and SW480 cells. Mechanistically, we found propofol treatment causes up-regulation of miR-361 and miR-135b, that suppress expression of STAT6 and thereafter leads to the inhibition of IL-13/STAT6/ZEB1 signaling pathway. In conclusion, our data for the first time demonstrated that propofol may serve as a novel therapeutic drug for targeting IL-13. The aggressive function of IL-13/STAT6/ZEB1 axis in colorectal cancer was impaired by propofol through miR-361 and miR-135b.