Road freight e-commerce platforms, as a specialized form of e-commerce in the road transportation sector, face complex operational risks due to their unique service positioning and business models. This study employs a comprehensive methodology to examine the risk framework of these platforms. Through the development of three distinct questionnaires, 20 critical risk factors are identified, which were subsequently analyzed using a combination of Decision-making Trial and Evaluation Laboratory (DEMATEL) and Interpretive Structural Modeling (ISM) approaches. Furthermore, a systematic risk assessment is conducted by integrating the Analytic Hierarchy Process (AHP) with Fuzzy Comprehensive Evaluation (FCE) methods. The research reveals that the 20 core risk factors affecting road freight e-commerce platforms exhibit a systematic and hierarchical structure, with clearly defined transmission pathways between different levels of risk factors. This investigation uncovers the internal interaction mechanisms among these risk factors. The study demonstrates that a thorough consideration of risk factor mechanisms, coupled with a systematic risk assessment, can significantly enhance the effectiveness and precision of risk control strategy formulation. This methodological approach not only provides a robust framework for understanding the complex risk landscape of online freight platforms but also offers practical insights for developing targeted risk mitigation strategies in this evolving sector.