To date, there have only been 46 patients reported in the literature with trisomy 18 and hepatoblastoma. We describe the case of an 11-month-old female with trisomy 18 and hepatoblastoma who was successfully treated by pairing surgical resection with a modified chemotherapy regimen omitting doxorubicin given her underlying cardiac abnormalities. Our case successfully demonstrates how chemotherapy regimens can be modified to accommodate for other underlying abnormalities and emphasizes that routine screening guidelines should exist for patients with trisomy 18 to allow for earlier detection and treatment.