Abstract: Objective To explore the predictive value of CT signs combined with serum abnormal plasminogen (PIVKA-Ⅱ) on microvascular invasion (MVI) in patients with isolated hepatocellular carcinoma. Methods A total of 97 patients with isolated hepatocellular carcinoma who underwent surgical treatment in Chongqing Kaizhou District People's Hospital from January 2021 to February 2023 were selected. All the patients underwent CT examination and serum PIVKA-Ⅱ test before surgery. Based on postoperative pathological results as the gold standards, they were divided into two groups: a MVI group and a non-MVI (n-MVI) group. Univariate analysis was performed, followed by multivariate logistic analysis to screen out the risk factors for MVI in patients with isolated hepatocellular carcinoma. Furthermore, receiver operating characteristic (ROC) curves were plotted to evaluate the predictive efficiency of CT signs combined with serum PIVKA-Ⅱ for MVI in patients with isolated hepatocellular carcinoma. Results According to postoperative pathological results, the incidence of MVI was 30.07% among 97 patients with isolated hepatocellular carcinoma. Compared with the n-MVI group, the MVI group showed statistical differences in tumor diameter, tumor margin, envelope type, halo sign, and serum PIVKA-Ⅱ (P<0.05). Multivariate logistic analysis indicated that tumor margin (OR=2.236), envelope type (OR=3.075), halo sign (OR=2.129), and serum PIVKA-Ⅱ (OR=2.528) were the independent risk factors for the development of MVI (P<0.05). The ROC curves presented that the area under the curve (AUC) of tumor margin, envelope type, halo sign, and serum PIVKA-Ⅱ alone for predicting MVI was 0.715, 0.763, 0.601, and 0.759, respectively, whereas the AUC of the above CT signs combined with serum PIVKA-Ⅱ for predicting MVI was 0.853 (95% CI: 0.739-0.967), with a sensitivity of 83.87%, a specificity of 78.79%, and an accuracy of 80.41%. Conclusions Isolated hepatocellular carcinoma patients with MVI present less smooth tumor margins, incomplete envelope, halo sign and other CT signs, with remarkably increased serum PIVKA-Ⅱ. The above mentioned CT signs combined with serum PIVKA-Ⅱ is effective in predicting MVI.