Objective To investigate the predictive value of the combination of cell cycle protein-dependent kinase inhibitor 3（CDKN3） and serum chitosanase 3-like protein 1（CHI3L1）， and microRNA-106b（miR-106b） assays in hepatocellular carcinoma metastasis. Methods One hundred patients with hepatocellular carcinoma admitted to the hospital between September 2019 and December 2023 were selected as study subjects and included in the hepatocellular carcinoma group， 87 patients with cirrhosis were included as the cirrhosis group during the same period， 96 patients with chronic hepatitis B as the chronic hepatitis B group， and 98 healthy persons undergoing routine physical examination were included in the healthy control group， and the groups were compared with respect to the serum CHI3L1， the cell-cycle molecule CDKN3， and the miR-106b levels. The hepatocellular carcinoma group was divided into 26 metastatic cases， 63 non-metastatic cases， and 11 cases lost to follow-up according to whether they metastasized during the 1-year follow-up period， and baseline data， cell cycle molecules CDKN3， miR-106b， and serum CHI3L1 levels were compared between the two groups. Risk factors for hepatocellular carcinoma metastasis were analyzed using multifactorial logistic， and the predictive value of the combined detection of miR-106b， the cell cycle molecule CDKN3， and serum CHI3L1 for hepatocellular carcinoma metastasis was analyzed using ROC curves. Results Compared with the healthy control group， the levels of CHI3L1， cell cycle molecule CDKN3， and serum miR-106b were elevated in the hepatocellular carcinoma group， chronic type B group， and cirrhosis group， and the chronic type B group < cirrhosis group < hepatocellular carcinoma group， which showed a tendency to be elevated with the increasing degree of liver disease， and the difference was statistically significant（P<0.05）. Compared with the non-metastatic group， the metastatic group had higher levels of alanine aminotransferase（ALT）， percentage of tumors >3 cm， CHI3L1， cytokinin A2（CCNA2）， percentage of tumors with stage > Ⅲ， the cell cycle molecule CDKN3， abnormal plasminogen， glutamyltransferase（GGT）， miR-106b， total bile acids（TBA）， alpha-fetoprotein（AFP）， number of tumors percentage of multiple occurrences， and glutamyltransferase（AST） levels were elevated， and the difference was statistically significant（P<0.05）. The results of multifactorial logistics analysis showed that the risk factors for hepatocellular carcinoma metastasis included ALT， CCNA2， tumor > 3 cm， AST， GGT， tumor stage > Ⅲ， AFP， CHI3L1， multiple tumors， abnormally high blood plasminogen， miR-106b， cell cycle molecule CDKN3， TBA. the results of the ROC curve analysis showed that miR -106b， serum CHI3L1， cell cycle molecule CDKN3 combined detection sensitivity was 93.65%， accuracy was 84.27%， and AUC value was 0.776 higher than the sensitivity， accuracy， and AUC value of single detection， and the difference was statistically significant（P < 0.05）. Conclusions Elevated levels of cell cycle molecule CDKN3， serum CHI3L1， and miR-106b are risk factors for liver cancer metastasis. It can be used to predict the occurrence of liver cancer metastasis， and the combined detection has significant predictive efficacy.