While the incidence of early-onset cancers is rising, it is unclear whether this is the case for early-onset hepatocellular carcinoma (eHCC). Even the definition of eHCC remains unclear. This study was designed to identify an age cutoff for eHCC and to explore trends in its incidence, clinical presentation, surgical outcomes, and long-term survival compared to typical-onset HCC (tHCC).

The National Cancer Database was queried for HCC patients (2010–2021). Both eHCC (< 50 years) and tHCC (≥ 50 years) were statistically defined. Propensity score matching adjustment, multivariate hazard ratios, and stage-dependent Kaplan-Meier survival analysis were calculated.

Among 207,653 patients, 10,128 (4.88%) had eHCC, with decreasing incidence from 2010 to 2021 (7.50% to 3.83%). eHCC had higher grade, synchronous metastasis, and nodal involvement. Independent predictors of worse 5-year survival included tHCC, uninsured, and higher TNM staging. Despite worse clinical characteristics, eHCC had improved survival across all stages (p < 0.001). After matching, eHCC had improved outcomes for stage I, II (p < 0.001, p = 0.004), and T1–T3 tumors (p < 0.001, p = 0.002, p = 0.045), but not T4. Minority status, lack of insurance, lower income, and greater distance to the hospital are independent predictors of eHCC.

After defining a novel, evidence-based age cutoff for eHCC, data indicate that while cancer incidence among younger patients is generally rising, the incidence of eHCC is declining. Although eHCC are more advanced cancers, they have improved outcomes compared to tHCC when undergoing surgery. In this context, especially young patients with stage I, II, or tumor ≤ T3 have favorable outcomes following resection.