Abstract: Objective  To investigate the effect of high-fat diet on liver metastasis of colon cancer and its underlying mechanism. Methods Xenograft models of nude mice were constructed based on the data of a total of 30 NSI third-generation immunodeficient nude mice，which were implanted with colon cancer cells DLD1 into their spleens. The xenograft nude mice were evenly divided into three groups：a control group，which was fed normal diet，a high-fat diet group，which was fed high-fat diet，and a high-fat diet+AMD3100 group，which was fed high-fat diet with intraperitoneal injection of CXCR4 antagonist AMD3100.  After 12 weeks，the nude mice in each group were sacrificed by cervical dislocation，and the weights of the bodies and livers of nude mice were monitored，and the number of tumor metastasis in the liver was counted. The protein and mRNA expression of SDF-1 and CXCR4 in tumor tissues of each group were detected by Western blot and RT-qPCR. Results After 12 weeks，the body weight，fat mass，liver weight，and serum leptin concentration of the nude mice in the high-fat diet group were significantly higher than those in the control group and the high-fat diet+AMD3100 group（P<0.05）. The proportion of liver metastasis in the control group，high-fat diet group，and high-fat diet+AMD3100 group nude mice were 30.0%，80.0%，and 40.0%，respectively. The tumor volume and the number of liver metastases in the high-fat diet group were significantly higher than those in the control group ［（3.83±0.42） mm³ vs （1.00±0.15） mm³，P<0.001； 4.33±0.58 vs 1.33±0.58，P=0.002］ and the high-fat diet+AMD3100 group ［（3.83±0.42） mm³ vs （1.96±0.15） mm³，P<0.001； 4.33±0.58 vs 2.33±0.58，P=0.002］. Western blot and RT-qPCR results showed that the protein and mRNA expression of SDF-1 and CXCR4 in colon cancer tissues in the high-fat diet group were significantly higher than those in the control group and the high-fat diet+AMD3100 group（P<0.05）. Conclusion High-fat diet can enhance liver metastasis of colon cancer by promoting the expression of SDF-1 and CXCR4 in colon cancer tissues.