Keeping regional railway transportation safe is of great importance for railway system engineers and decision makers. However, there are still great challenges in modeling the complicated conditions in regional railway transportation: (1) Multiple types of data and knowledge in complicated correlations need to be analyzed, and (2) The approach must be open and accessible to decision makers so that a balanced decision can be made. To address the above challenges, a safety assessment approach using the hybrid Belief Rule Base (BRB) is proposed. In the new approach, multiple types of information are modeled under the hybrid assumption, and thus, hybrid rules are constructed to form the hybrid BRB. With this, both data and knowledge in complicated correlations can be used for the safety assessment on regional railway transportation, rather than only a single railway station or equipment component. Moreover, the assessment process remains open and accessible which provides good interpretability to stakeholders. An empirical regional railway safety assessment case is studied on the existing line and high speed line in the Cheng-Yu region located in the southwestern China. Five aspects, namely, the environment, equipment, management, passengers, and accident, are analyzed and then disintegrated into sub-factors. With the aspects and sub-factors, a comprehensive model is constructed. Case study results show that (1) the overall safety levels of the high speed line are better than the existing line, (2) the safety assessment results are consistent with the historical reports of accidents and system failures, (3) among all aspects, the environment and equipment have a more direct effect on the overall safety levels, and (4) consistency has also been found with railway accident statistics collected from Japan and Canada.