Nb is a key alloying element added into X80 pipeline steel, and it can enhance mechanical properties by refining grains and introducing precipitates. However, HIC resistance is also one of the most significant performances for pipeline steel served in H2S environment. An all-inclusive recognition of the response of niobium to HIC refusal is important for the appropriate design of the Nb addition amount, the rolling and cooling parameters, and protective techniques to obtain excellent mechanical properties, including strength and ductility and HIC refusal. So in the paper, many test methods, such as EBSD, SEM, and HIC, were adopted to research the response of niobium addition on resistance of hydrogen-induced cracking performance of X80. As the increase in Nb content, grain size decreased and had the strongest trapping hydrogen atom ability. Besides, the percentage of low-angle grain boundaries went up, and more precipitates greatly raised the amount of irreversible hydrogen pitfalls. Nb could greatly promote the HIC resistance, inhibiting crack initiation, and propagation.