Debris avalanches caused by landslides often lead to building damage, and insufficient research has been conducted on the vulnerability of buildings, especially reinforced concrete (RC) buildings, to such impact disasters. Here, a vulnerability assessment framework for a two-story RC building based on the generalized F-discrepancy (GF-discrepancy)-based point selection strategy and discrete element method (DEM)-finite element method (FEM) is proposed. Considering the randomness of granular flow, including the impact height, impact velocity, and density, these three random variables are uniformly selected using GF-discrepancy, for a total of 134 samples. A deterministic analysis of each sample is performed to obtain the responses of the 134 samples according to the DEM-FEM coupling method, which can fully reflect the failure characteristics of RC buildings under mass flow impact. Given the qualitative vulnerability assessment, we select the inter-story displacement angle and the displacement of walls and columns in the responses as quantitative indicators defining the four damage states and the vulnerability of the building. The former is used to evaluate the overall damage state of the building, while the latter is applied to evaluate the local damage situation of the building as a correction to the first indicator. Ultimately, the vulnerability of the building is obtained corresponding to different impact indictors related to three random variables. This method provides not only the vulnerability of RC buildings under particle flow impact but also insight into vulnerability assessments of buildings in areas that are not currently in danger of such disasters.