The reference engineering design of the IFMIF-DONES nuclear Heating, Ventilation, and Air Conditioning system (HVAC) has been analyzed in terms of potential failure modes and consequences as well as life-cycle reliability and availability. The HVAC system performs the safety function of preventing lithium fire and uncontrolled releases of radioactive materials from the radiological areas. The results of the Reliability, Availability, Maintainability and Inspectability (RAMI) analysis are of high practical importance for future activities on the system optimization and safety demonstration. This paper proposes a unified approach to the Failure Mode and Effects Analysis (FMEA) that can be applied to the plant systems evaluation in terms of the failure frequency, severity, and detectability. The reliability and availability calculation has been performed for two sets of data, the U.S. NRC collection representing the industry standards of fission power plants, and the fusion-specific data gathered from several sources and integrated by Monte Carlo-based method. Inherent availability of above 99.4% has been reached for the HVAC system based on the fusion-specific data. The use of reliability data from the commercial fission plants increased the system availability to nearly 99.8%, thus indicating the potential for allocation of higher availability requirements to the HVAC functions.