Background: Combined hepatocellular-cholangiocarcinoma (CHC) is a rare but vital heterogeneous histological subtype of primary liver cancer (PLC) with no standardized treatment strategy. This study aimed to preliminarily investigate the role of liver transplantation (LT) in CHC and develop a novel risk scoring model (RSM) to evaluate the benefits of transplantation. Methods: The study cohort was taken from the Surveillance, Epidemiology, and End Results database. The annual percent change (APC) in incidence or ratio was calculated utilizing the Joinpoint regression. Propensity score matching (PSM) was introduced to reduce the selection bias between groups. A novel RSM was developed based on the independent prognostic factors identified by the Cox regression model. The predictive performance of the RSM was compared with the Milan Criteria and the University of California, San Francisco (UCSF) Criteria, respectively. Results: A total of 223 CHC patients were enrolled, and 60 (26.9%) of them received LT. The incidence-based mortality did not decrease between 2004 and 2015 (APC =1.7%, P=0.195). Although LT was considered an independent protective predictor for CHC, it showed a declining ratio from 33.3% in 2004 to 15.4% in 2015 (APC =-8.9%, P=0.012). The LT recipients had better outcomes than others who underwent hepatectomy or local destruction (P<0.05). Compared with other subtypes of PLC, the post-transplantation prognoses of CHC patients were similar to those with hepatocellular carcinoma (P>0.05) but significantly better than those with intrahepatic cholangiocarcinoma (ICC) (P<0.05). Based on the RSM (vascular invasion: 1 point; tumor size >2 cm: 1 point; multiple tumors: 2 points), patients were stratified into two prognostic subgroups: the low-risk (scoring ≤2) and the high-risk (scoring >2 or extrahepatic metastasis) groups. Patients in the low-risk group were more likely to benefit from LT. The predictive performance of the RSM outperformed the Milan and UCSF Criteria in both the training and validation sets. Conclusions: Therapeutic strategies for CHC should be further improved. Patients with CHC should also be considered potential LT candidates. The novel RSM could be helpful to stratify patients and assist clinical decision-making.