This work presents the influence of microstructural constituents on liquation crack formation in the cast Ni-based superalloy, René 108. The investigation was divided into three parts: characterisation of the material's microstructure in pre-weld condition, hot ductility studies and analysis of liquation cracking induced by the gas tungsten arc welding process. Using advanced electron microscopy techniques it is shown that the base material in pre-weld condition is characterised by a complex microstructure. The phases identified in René 108 include γ matrix, γ' precipitates, MC and M23C6 carbides, and M5B3 borides. Based on Gleeble testing, it was found that René 108 is characterised by high strength at elevated temperatures with a maximum of 1107 MPa at 975 °C. As a result of constitutional liquation, the superalloy’s strength and ductility were significantly reduced. The nil strength temperature was equal to 1292 °C, while the nil ductility temperature was 1225 °C. The low ductility recovery rate (32.1), ratio of ductility recovery (36.2) and hot cracking factor (Rf = 0.05) values confirmed the low weldability of Renѐ 108. In the heat-affected zone (HAZ) induced by welding, constitutional liquation of mainly γ' precipitates, with a contribution of M23C6 carbides and M5B3 borides, was observed. The thin non-equilibrium liquid film, which formed along high-angle grain boundaries, led to crack initiation and their further propagation during cooling. The eutectic γ–γ' re-solidification products are visible on the crack edges.