BACKGROUND Some patients with hepatocellular carcinoma (HCC) are more likely to experience disease progression despite continuous transarterial chemoembolization (TACE), which is called TACE refractoriness. At present, it is still difficult to predict TACE refractoriness, although some models/scoring systems have been developed. At present, radiological-based radiomics models have been successfully applied to predict cancer patient prognosis. OBJECTIVE To develop and validate a computed tomography (CT)-based radiomics nomogram for the pre-treatment prediction of TACE refractoriness. METHODS This retrospective study consisted of a training dataset (n = 137) and an external validation dataset (n = 81) of patients with clinically/pathologically confirmed HCC who underwent repeated TACE from March 2009 to March 2016. Radiomics features were retrospectively extracted from preoperative CT images of the arterial phase. The pre-treatment radiomics signature was generated using least absolute shrinkage and selection operator Cox regression analysis. A CT-based radiomics nomogram incorporating clinical risk factors and the radiomics signature was built and verified by calibration curve and decision curve analyses. The usefulness of the CT-based radiomics nomogram was assessed by Kaplan-Meier curve analysis. We used the concordance index to conduct head-to-head comparisons of the radiomics nomogram with the other four models (Assessment for Retreatment with Transarterial Chemoembolization score; α-fetoprotein, Barcelona Clinic Liver Cancer, Child-Pugh, and Response score; CT-based radiomics signature; and clinical model). All analyses were conducted according to the transparent reporting of a multivariable prediction model for individual prognosis or diagnosis statement. RESULTS The median duration of follow-up was 61.3 mo (interquartile range, 25.5-69.3 mo) for the training cohort and 67.1 mo (interquartile range, 32.4-71.3 mo) for the validation cohort. The median number of TACE sessions was 4 (range, 3-7) in both cohorts. Eight radiomics features were chosen from 869 candidate features to build a radiomics signature. The CT-based radiomics nomogram included the radiomics score (hazard ratio = 3.9, 95% confidence interval: 3.1-8.8, P < 0.001) and four clinical factors and classified patients into high-risk (score > 3.5) and low-risk (score ≤ 3.5) groups with markedly different prognoses (overall survival: 12.3 mo vs 23.6 mo, P < 0.001). The accuracy of the nomogram was considerably higher than that of the other four models. The calibration curve and decision curve analyses verified the usefulness of the CT-based radiomics nomogram for clinical practice. CONCLUSIONS The newly constructed CT-based radiomics nomogram can be used for the pre-treatment prediction of TACE refractoriness, which may provide better guidance for decision making regarding further TACE treatment.