Primary hepatic squamous cell carcinoma (SCC) is a rare malignancy with aggressive clinical features. This is the first case report of a primary hepatic SCC diagnosed by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), which is a reliable and safe procedure for the histopathological diagnosis of liver lesions, even if the percutaneous approach is difficult due to ascites or hypervascularity at the puncture site. A 52-year-old man presented to the emergency department of a tertiary referral hospital with right upper quadrant abdominal pain and abdominal distention. Given the laboratory data, a diagnosis of spontaneous bacterial peritonitis (SBP) was made. Concurrently, an abdominal computed tomography (CT) scan revealed an 8 cm hypodense mass with delayed peripheral enhancement in the left hepatic lobe and paraaortic and perihepatic lymphadenopathy. As persistent ascites precluded percutaneous liver biopsy, we performed EUS-FNA of the liver mass, and the obtained specimen showed SCC. As otorhinolaryngological consultation and whole-body investigations, including chest CT, upper and lower endoscopy, and positron emission tomography CT, were all unremarkable except for the liver lesion and lymph nodes, a diagnosis of primary hepatic SCC with systemic lymph node metastasis was made. After treatment of SBP with antibiotics, we initiated chemotherapy concurrent with radiation therapy, adapted to his liver function. Radiation and three cycles of chemotherapy were not effective as the disease progressed, as seen on the follow-up CT scan, and the patient died of hepatic failure on the 134th day after diagnosis. In conclusion, EUS-FNA was a reliable method for tissue sampling in liver malignancies, particularly in selected patients with contraindications for percutaneous biopsy.