Intra-tumoral tertiary lymphoid structures (TLSs) are associated with a favorable prognosis for patients with hepatocellular carcinoma (HCC). We aimed to identify image features related to TLSs and develop a nomogram for preoperative noninvasive prediction of intra-tumoral TLSs.This retrospective study enrolled patients with HCC who underwent contrast-enhanced computed tomography before surgery between January 2014 and September 2020. Two radiologists retrospectively and independently reviewed the CT imaging features, and interobserver agreement was assessed. Univariable and multivariable logistic regression analyses were applied to investigate clinical laboratory data and imaging features related to TLSs. A regression-based predictive model and nomogram were constructed using the identified predictors. Nomogram diagnostic performance was assessed with the area under the receiver operating characteristic curve (AUC) and calibration curves, and validated using 5-fold cross-validation.Ninety-three of the 142 HCCs were TLS + HCCs. Multivariable analyses identified intratumor arteries (odds ratio [OR]: 0.23; 95% confidence interval [CI]: 0.07-0.63; p = 0.007), intratumor hemorrhage (OR: 0.08; 95% CI: 0.01-0.50; p = 0.012), positive HBsAg or HCVAB status (OR: 4.52; 95% CI: 1.65-13.29; p = 0.004), platelet count (≥186.5 × 109 /L, OR: 0.38; 95% CI: 0.16-0.86; p = 0.022), and aspartate transaminase level (≥33.2 IU/l, OR: 0.24; 95% CI: 0.09-0.59; p = 0.003) as independent predictors of intra-tumoral TLSs. AUC of the regression-based model was 0.79 (95% CI:0.72-0.86) and average AUC at 5-fold cross-validation was 0.75 (95% CI: 0.71-0.80).CT-based nomogram is promising for preoperative prediction of intra-tumoral TLS in HCC.Copyright © 2022 Elsevier B.V. All rights reserved.