Aim To investigate the individualized survival benefit of hepatic arterial infusion chemotherapy (HAIC) and sequential ablation treatment in large hepatocellular carcinoma (HCC) patients. Methods Between February 2016 and December 2020, a total of 228 HCC patients (diameter > 5 cm) who underwent HAIC alone (HAIC group, n = 135) or HAIC and sequential ablation (HAIC-ablation group, n = 93) treatment were reviewed. We applied the inverse probability of treatment weighting (IPTW) to adjust for potential bias of two treatment groups. The overall survival (OS) and progression-free survival (PFS) were compared with Kaplan–Meier curves. The Cox regression model was used to identify independent prognostic factors. And a prediction nomogram based on these independent prognostic factors was built, aiming to make probabilistic survival predictions and estimate personalized ablation benefits. Results After a median follow-up of 17.9 months, HCC patients in the HAIC-ablation group have longer significantly OS and PFS than those in the HAIC alone group (median OS: 22.2 months vs. 14.5 months; median PFS: 8.5 months vs. 4.6 months; both, p < 0.001). The IPTW-adjusted analysis revealed similar findings (both, p < 0.001). Tumor size, tumor number, and treatment modality were identified as independent prognostic factors for OS. The nomogram based on these factors showed favorable discrimination and well calibration. Conclusions HAIC and sequential ablation provided significant survival benefits in patients with large HCC. The nomogram could help predict individual survival probabilities and estimate personalized sequential ablation benefits.