Safety is a fundamental and transversal discipline throughout the design, construction, operation, and eventual decommissioning of the IFMIF-DONES facility, which will be classified as a Category 1 Radioactive Installation according to the Spanish law. The singularity and one-of-a-kind characteristics of IFMIF-DONES (both in Spain and worldwide) requires the development of an ad-hoc Safety Approach and Licensing Strategy that guarantees Safety to Personnel, Public and the Environment with very low acceptable risks, following the uppermost standards while keeping an optimized balance with the associated technological complexity and feasibility. This work provides a comprehensive overview of this Approach and Strategy that is being developed, involving: (i) Top-level Safety regulations and the adapted methodology to apply them to the singularities of IFMIF-DONES, including dose and risk limits to public and workers. (ii) Engineering inputs necessary to implement the radiological safety engineering approach, such as material-at-risk, Hazard Categorization and Seismic aspects. (iii) Methodology for the hazard analysis through the identification and study of Reference Accident Scenarios, definition of lines-of-defense, Safety Important Class Systems, Structures and Components (SIC-SSCs) and their requirements. (iv) Description of the SIC-SSCs that are being implemented from an engineering perspective, such as confinement barriers, safety interlocks, area classifications, access controls and radiation monitoring. (v) Implementation of ALARA principles from the design phase to reduce the occupational radiation exposure of workers to fulfill the targets of maximum individual and collective dose during operation. (vi) Experimental programs ongoing to support Safety aspects. This work paves the way for the next stages in the development of the IFMIF-DONES facility and program.