The fracture mechanism of hydrogen charged Ti-6Al-4V has been investigated through a multianalytical approach. The difference in hydrogen solubility between 13 phase (high solubility) anda phase (low) governs the formation and growth pattern of titanium hydrides, and determine the fracture mode of Ti-6Al-4V. Depending on the hydrogen charging extent, the penetration of hydrogen and distribution of hydrides can be divided into three stages. In the initial stage hydrogen diffuses mainly into the 13 phase, as judged from its increase in Volta potential, and with no hydrides formed. Failure analysis after tensile tests exhibits plastic behavior and a fracture surface with mainly dimples. In the subsequent transition stage, hydrides are formed at the a/13 interfaces and along a grain boundaries. More initial cracks occur in the brittle hydrides and the fracture surface transforms from dimple to quasi-cleavage. In the final stage a layer of uniformly distributed hydride is produced on the surface and within the a phase. Supported by nanoindentation measurements, the plasticity of the charged sample diminishes with hydrogen charging time, and an intergranular-transgranular mixed fracture is observed. Overall, the study forms clear evidence that the distribution and cracks of hydrides influence the fracture mode of the Ti-6A-4V alloy.