Stainless steel (SS) samples were irradiated with protons at 400°C and strained in 288°C water to examine the role of oxide particles in the irradiation-assisted stress corrosion cracking (IASCC) process. Oxides in the matrix acted as the predominant crack initiation sites, and the amount of cracking scaled with oxide density. Intergranular cracking occurred by mechanical failure of oxide particles that created electrochemical crevices and stress concentrators from which intergranular cracks could propagate. Relatively few of the cracked oxide particles actually led to intergranular cracking in the matrix, which was consistent with the requirement that the crack tip solution had to be deaerated for an aggressive crevice chemistry to form and that the cracks in the oxides had to be well aligned with susceptible grain boundaries. Intergranular cracking occurred only when both the SS was irradiated and when straining was conducted in high-temperature water. This observation supported an IASCC mechanism that required an aggressive environment and an irradiated microstructure.