316 stainless steel (316SS) is widely used due to a combination of good mechanical properties and excellent corrosion resistance. However, the intergranular stress corrosion cracking (IGSCC) is a serious problem for 316SS exposed to aggressive environments, which could result in unexpected failures and lead to huge losses. The grain boundary structure and local stress applied on the grain boundary are proved to have significant influence on the initiation of the IGSCC. In this work, thermal-mechanical processing was applied to the 316SS to yield a large-grained sample. The sample plates with a single-grained thickness were subjected to three-points bending SCC tests in an acidified boiling 25%NaCl solution. The result shows that the random grain boundaries (GBs) have the highest propensity to IGSCC initiation, while the Σ3 GBs shows very low tendency to IGSCC initiation. The absolute values of Schmid factor mismatch (Δm) between the grains on both sides of the GBs were analyzed for a large number of GBs. The distribution of the Δm for the Σ3 GBs is obviously different from that of the random GBs. The Δm has significant influence on the IGSCC susceptibility in the range of 0<Δm<0.1. The larger value of the Δm, the higher propensity for the IGSCC initiation at the GBs, for both the random GBs and the Σ3 GBs.