This study investigated the effects of deep cryogenic treatment applied to M42 HSS drills on the tool wear, the tool life and the surface roughness during the drilling of a Ti-6Al-4V alloy under dry and wet cutting conditions. Drilling tests were carried out using untreated, cryogenically treated, cryogenically treated and tempered, and multi-layered TiAlN/TiN-coated HSS drills. Four different cutting speeds ((6, 8, 10, 12) m/min) and a constant feed rate of 0.06 mm/r were used as the cutting parameters and holes with a depth of 15 mm were drilled. At the end of the drilling tests, it was seen that the use of a coolant increased the tool life and decreased the surface roughness. Among the four tools, the best results in terms of the tool life and surface roughness were obtained with the multi-layered TiAlN/TiN-coated tool. The cryogenically treated and tempered drills exhibited an increase of 87 % in the tool life compared to the untreated drills. Scanning electron microscope (SEM) and X-ray diffraction (XRD) analyses showed that by reducing the size of the carbide particles in the microstructure, cryogenic treatment resulted in a more uniform carbide distribution and in the transformation of retained austenite to martensite. This played an important role in the increase in the hardness and wear resistance of the cutting tools.