The incidence of inter-city bus accidents receives a lot of attention from the public because they often cause heavy casualties. The Human Factors Analysis and Classification System (HFACS) is the prevailing tool used for traffic accident risk assessment. However, it has several shortcomings, for example: (1) it can only identify the potential failure modes, but lacks the capability for quantitative risk assessment; (2) it neglects the severity, occurrence and detection of different failure modes; (3) it is unable to identify the degree of risk and priorities of the failure modes. This study proposes a novel hybrid model to overcome these problems. First, the HFACS is applied to enumerate the failure modes of inter-city bus operation. Second, the Z-number-based best–worst method is used to determine the weights of the risk factors based on the failure mode and effects analysis results. Then, a Z-number-based weighted aggregated sum product Assessment is utilized to calculate the degree of risk of the failure modes and the priorities for improvement. The results of this study determine the top three ranking failure modes, which are personal readiness from pre-conditions for unsafe behavior, human resources from organizational influence, and driver decision-making error from unsafe behavior. Finally, data for inter-city buses in Taiwan in a case study to illustrate the usefulness and effectiveness of the proposed model. In addition, some management implications are provided.