【Objective】In order to ensure the timely arrival of goods and enhance the reliability of cold chain road-rail intermodal transport, this paper addresses path optimization under conditions of varying demand. 【Method】The concept of path time reliability was introduced under uncertain time conditions, with the reliability of a route scheme defined as the minimum time reliability of all paths. A multi-objective optimization model was constructed with the goals of minimizing total transportation cost, minimizing carbon emissions, and maximizing reliability. The model was solved using the NSGA-Ⅱ combined with an elite strategy to compute examples, analyzing the effects of different reliability strategies and uncertain timing on route optimization.【Result】The optimized model focused on reliability achieves an average reliability close to 0.9, with a broader distribution of Pareto solutions. The impact of uncertain road transportation time on reliability is more significant compared to uncertain waiting transfer times.【Conclusion】The optimization model proposed in this paper effectively provides high-reliability paths to meet the needs of different carriers.