Introduction Hepatoblastoma has a low annual incidence (1.7/1,000,000 children) posing a barrier to studying epidemiologic risk factors in its development. Current accepted associations include low birthweight and overgrowth syndromes. Neonatal intensive care unit (NICU) interventions were evaluated for the relationship with subsequent development of hepatoblastoma. Methods Pediatric Health Information System data between 2016-2022 was queried for all NICU admissions. From this set, patients with a diagnosis code for hepatoblastoma were identified. Pharmacy billing information was used to calculate total number of days of total parenteral nutrition (TPN) and mechanical ventilation exposure during NICU hospitalization. Results 293,681 patients met inclusion, with 51 patients diagnosed with hepatoblastoma. Logistic regression demonstrated that every 10 additional days of TPN (OR 1.10, 95% CI 1.00-1.13) or mechanical ventilation (OR 1.08, 95% CI 1.06-1.09) was correlated with increased likelihood of development of hepatoblastoma. The dataset was partitioned into two samples, one for training and the other for validation. TPN and duration of mechanical ventilation were the retained predictors within the training sample following least absolute shrinkage and selection operator analysis. Using these retained predictors within the validation sample, there were 773 patients with a predicted probability of developing hepatoblastoma greater than 0.05%, with 6 patients who developed hepatoblastoma (0.78%). Discussion A cohort of infants were identified as having a risk for the subsequent development of hepatoblastoma, similar to that of patient with known associated syndromes. A predictive model was created to assist in identifying patients who may benefit from screening based upon specific NICU exposures.