Background: The global incidence and mortality rates of liver cancer, which is the second leading cause of cancer-related deaths worldwide, are increasing. However, information on its epidemiology and clinical prognosis is limited. This study aimed to characterize the epidemiology and prognostic factors of secondary liver cancer to aid in the pretreatment evaluation of the disease. Methods: Patients diagnosed with secondary liver cancer between 2010 and 2014 in the Surveillance, Epidemiology, and End Results (SEER) database were retrospectively included. Kaplan-Meier analysis and Multivariate Cox regression analysis were performed to screen for significant factors associated with secondary liver cancer. Results: A total of 85,738 secondary liver cancer patients were identified; in this population, the first primary site was the lung (25.9%), followed by the colorectum, pancreas, stomach, breast, and cecum. Patients with primary tumors of the colorectum, cecum and breast had longer median survival time. Advanced age, male gender, black race, poor differentiation or lack of differentiation, regional lymph node metastases, and presence of distant metastasis were associated with poor prognosis. Conclusions: In this study, novel findings on the role of the primary site and synchronous distant metastasis to specific organs in patients with secondary liver cancer were described. These findings have significant implications in clinical diagnosis and treatment, and provide a better understanding of secondary liver cancer in the general population.