ABSTRACT An in-depth understanding of the role of non-metallic inclusions (NMIs) in the hydrogen-induced failure of structural materials is important in the manufacture and application of steels. In this paper we investigated the type, the amount and the distribution of NMIs in pipeline steels and their relation to the susceptibility to hydrogen-induced cracking (HIC). Scanning Electron Microscope (SEM) observation confirmed the interlinking of the microcracks formed at the inclusion-matrix interfaces. By combining with the nondestructive three-dimensional (3D) mapping of crack propagation paths, based on the synchrotron tomography technique, we obtained direct evidence that the cracking initiation at the NMIs and then interlinking on the (nearly) same plane are the main mechanism of HIC failure in X70 steels. We built an elastic-energy-based model, which can be applied to quantitatively predict the HIC-induced dependence of the fracture toughness on NMIs, based on statistical information of the NMIs. The theoretical results show a good agreement with the experimental observation. We proposed a criterion to determine the susceptibility to HIC by the observation of NMIs. We also developed a thermodynamics-based model to analyze the hydrogen trapping at the inclusion-matrix interface and its dependence on the strength of the steel matrix. For the first time, the direct relationship between NMIs and HIC-induced degradation of fracture toughness is obtained.