<p>This study presents a case of primary hepatic small cell neuroendocrine carcinoma (PHNEC). The patient was a 74-year-old male with a history of hepatitis C virus (HCV) infection, who presented with persistent right upper quadrant and lower back pain for two weeks. Imaging studies revealed multiple nodules and masses in the left hepatic lobe, accompanied by enlargement of lymph nodes at the hepatic hilum and in the retroperitoneum. Subsequent liver biopsy was performed, and to rule out potential origins from the gastrointestinal tract or lungs, gastrointestinal endoscopy and chest computed tomography (CT) scans were conducted. These evaluations confirmed the diagnosis of hepatic small cell neuroendocrine carcinoma. Following one cycle of chemotherapy combined with localized radiotherapy, a reduction in the size of both lymph nodes and hepatic lesions was observed, achieving a partial response (PR). However, follow-up imaging one month later showed significant enlargement of the hepatic masses, indicating progressive disease (PD). Subsequent chemotherapy was withheld due to progressive hepatic dysfunction and superimposed infection. The patient ultimately succumbed to multi-organ failure, with an overall survival of 4 months. The imaging features of PHNEC are nonspecific, making diagnosis relatively challenging. Improving detection rates and establishing standardized treatment guidelines remain critical challenges for clinicians. We hope this case may serve as a reference for clinicians in the field and recommend close monitoring of serological markers of liver function throughout the entire course of treatment and follow-up.</p>