The mission of nuclear safety authorities in national radioactive waste disposal programmes is to ensure that people and the environment are protected against the hazards of ionising radiations emitted by the waste.It implies the establishment of safety requirements and the oversight of the activities of the waste management organisation in charge of implementing the programme.In Belgium,the safety requirements for geological disposal rest on the following principles:defence-in-depth,demonstrability and the radiation protection principles elaborated by the International Commission on Radiological Protection(ICRP).Applying these principles requires notably an appropriate identification and characterisation of the processes upon which the safety functions fulfilled by the disposal system rely and of the processes that may affect the system performance.Therefore,research and development(R&D)on safety-relevant thermo-hydro-mechanical-chemical(THMC)issues is important to build confidence in the safety assessment.This paper points out the key THMC processes that might influence radionuclide transport in a disposal system and its surrounding environment,considering the dynamic nature of these processes.Their nature and significance are expected to change according to prevailing internal and external conditions,which evolve from the repository construction phase to the whole heatingecooling cycle of decaying waste after closure.As these processes have a potential impact on safety,it is essential to identify and to understand them properly when developing a disposal concept to ensure compliance with relevant safety requirements.In particular,the investigation of THMC processes is needed to manage uncertainties.This includes the identification and characterisation of uncertainties as well as for the understanding of their safety-relevance.R&D may also be necessary to reduce uncertainties of which the magnitude does not allow demonstrating the safety of the disposal system. The mission of nuclear safety authorities in national radioactive waste disposal programs is to ensure that people and the environment are protected against the hazards of ionising radiations emitted by the waste. It implies the establishment of safety requirements and the oversight of the activities of the waste management organisation in charge of implementing the program. In Belgium, the safety requirements for geological disposal rest on the following principles: defense-in-depth, demonstrability and the radiation protection principles elaborated by the International Commission on Radiological Protection (ICRP) .Applying these principles requires notably an appropriate identification and characterisation of the processes upon which the safety functions fulfilled by the disposal system rely and of the processes that may affect the system performance. wherefore, research and development (R & D) on safety-relevant thermo-hydro-mechanical- chemical (THMC) issues is important to build confidence in the safety assessment. This paper points out the key THMC processes that might influence radionuclide transport in a disposal system and its surrounding environment, considering the dynamic nature of these processes. The nature and significance are expected to change according to prevailing internal and external conditions, which evolve from the repository construction phase to the whole heatingecooling cycle of decaying waste after closure. As these processes have a potential impact on safety, it is essential to identify and understand them well when developing a disposal concept to ensure compliance with relevant safety requirements In particular, the investigation of THMC processes is needed to manage uncertainties. This includes the identification and characterization of uncertainties as well as for the understanding of their safety-relevance. R & D may also be necessary to reduce uncertainties of which the magnitude does not allow demonstrating the safety of the disposal system.