A conventional process design lifecycle starts with a screening process of alternative chemical reaction pathways until the detailed design of the entire plant. During the design of the process, mainly the flow diagram of the process, errors may arise due to wrong decisions and basis made such as unsuitable process condition, construction material and etc., which will later cause problems to the following stages of the process lifecycle. Despite the availability of various methods, a proper detailed framework which guides users in selecting the appropriate method for their safety assessment based on input data availability is still missing. Therefore, this paper aims to address the above issue by proposing a systematic framework for safety assessment based on process information generated from PFDs during the preliminary design stage. The research on R & D and basic engineering design is currently on-going to develop the entire framework and will be presented in other papers. Technically, the framework is developed based on the methods screened to be suitable for application within the PFD-based context in any chemical processing plant. The framework also provides recommendations on the strategies for reducing the safety hazard and risk in the process in the respective design stage. A case study on process design of biorefineries is conducted to illustrate the functionality and benefit of the proposed framework. © 2022 American Institute of Physics Inc.. All rights reserved.