The paper presents the problem of coupling the gas flow dynamics in pipelines with the thermodynamics of hydrogen solubility in steel for the estimation of the fracture toughness. In particular, the influence of hydrogen blended natural gas transmission on hydrogen solubility and, consequently, on fracture toughness is investigated with a focus on the L485ME low-alloy steel grade. Hydraulic simulations are conducted to obtain the pressure and temperature conditions in the pipeline. The hydrogen content is calculated from Sievert’s law and, as a consequence, the fracture toughness of the base metal and heat-affected zone is estimated. Experimental data is used to define hydrogen-assisted crack size propagation in steel as well as to a plane strain fracture toughness. The simulations are conducted for a real natural gas transmission system and compared against the threshold stress intensity factor. The results showed that the computed fracture toughness for the heat-affected zone significantly decreases for all natural gas and hydrogen blends. The applied methodology allows for identification of the hydrogen-induced embrittlement susceptibility of pipelines constructed from thermomechanically rolled tubes worldwide most commonly used for gas transmission networks in the last few decades.