In situ observations of crack propagation in sulfur-doped coarse-grained nickel were performed for the specimens with grain boundary microstructure pre-determined by SEM/EBSD analysis. The role of grain boundary microstructure was studied in the crack propagation in nickel embrittled by grain boundary segregation of sulfur. It was found that the main crack tends to predominantly propagate along random boundaries, and the crack propagation rate can be locally accelerated at the grain boundary network with a high connectivity of random boundaries. On the other hand, the cracks can propagated along fracture-resistant low-I pound coincidence site lattice (CSL) boundary only when the trace of the grain boundary is arranged being almost parallel to slip bands in the adjacent grains. The local crack propagation rate was found to become lower when a crack propagated along low-I pound CSL boundaries. Moreover, when the crack propagation is inhibited by low-I pound CSL boundaries, the branching of propagating crack occurs at partially cracked triple junctions. The crack propagation can locally slow down due to the occurrence of crack branching. The optimum grain boundary microstructure for the control of sulfur segregation-induced brittle fracture is discussed on the basis of new findings obtained from the in situ observations on crack propagation and fracture processes in polycrystalline nickel.