This paper presents a seismic safety assessment method for train-bridge coupled (TBC) systems using non-Gaussian random processes. The method combines the new point estimate method (NPEM) with moment expansion approximation (MEA) to efficiently analyze the random responses of TBC systems under seismic conditions. The NPEM-MEA method is validated using the Monte Carlo method, demonstrating its accuracy and efficiency. A recommended truncation order of four to six is suggested for the NPEM-MEA. The study also discusses the influences of seismic magnitude and epicentral distance on the dynamic responses of the TBC system. The methodology not only facilitates seismic safety assessments for TBC systems but also contributes to standard-setting for these systems under earthquake conditions. The TBC system consists of simply supported beam bridges and is subjected to complex vibrations from ambient excitations, such as earthquakes. Earthquakes are unpredictable random factors that pose serious threats to trains and bridges, especially considering the long operation time of the high-speed railway (HSR) network. The random distributions of parameters in the TBC system differ from deterministic dynamic analysis. While most parameters in the TBC system follow normal or lognormal distributions, many critical parameters in seismic analysis, such as seismic magnitude (SM) and epicentral distance (ED), follow non-Gaussian distributions. Therefore, a compatible and efficient approach is necessary for seismic safety assessment in TBC systems. In this paper, the NPEM is applied to fast calculate statistical moments of system responses based on the Gaussian integral method. Furthermore, the MEA is introduced to obtain the probability density functions (PDFs) of the system responses based on calculated statistical moments. Thus, the statistics can be deduced according to the obtained PDFs. Consequently, the NPEM combined with the MEA (NPEM-MEA) can solve the probabilistic analysis with non-Gaussian processes. More than that, the NPEM-MEA can be helpful for the standard-setting of TBC systems under earthquakes. In addition, the MEA is applicable to the stochastic methods that can calculate the original moment.This paper presents a seismic safety assessment method for train-bridge coupled (TBC) systems using non-Gaussian random processes. The method combines the new point estimate method (NPEM) with moment expansion approximation (MEA) to efficiently analyze the random responses of TBC systems under seismic conditions. The NPEM-MEA method is validated using the Monte Carlo method, demonstrating its accuracy and efficiency. A recommended truncation order of four to six is suggested for the NPEM-MEA. The study also discusses the influences of seismic magnitude and epicentral distance on the dynamic responses of the TBC system. The methodology not only facilitates seismic safety assessments for TBC systems but also contributes to standard-setting for these systems under earthquake conditions. The TBC system consists of simply supported beam bridges and is subjected to complex vibrations from ambient excitations, such as earthquakes. Earthquakes are unpredictable random factors that pose serious threats to trains and bridges, especially considering the long operation time of the high-speed railway (HSR) network. The random distributions of parameters in the TBC system differ from deterministic dynamic analysis. While most parameters in the TBC system follow normal or lognormal distributions, many critical parameters in seismic analysis, such as seismic magnitude (SM) and epicentral distance (ED), follow non-Gaussian distributions. Therefore, a compatible and efficient approach is necessary for seismic safety assessment in TBC systems. In this paper, the NPEM is applied to fast calculate statistical moments of system responses based on the Gaussian integral method. Furthermore, the MEA is introduced to obtain the probability density functions (PDFs) of the system responses based on calculated statistical moments. Thus, the statistics can be deduced according to the obtained PDFs. Consequently, the NPEM combined with the MEA (NPEM-MEA) can solve the probabilistic analysis with non-Gaussian processes. More than that, the NPEM-MEA can be helpful for the standard-setting of TBC systems under earthquakes. In addition, the MEA is applicable to the stochastic methods that can calculate the original moment.