Abstract: Regional seismic risk quantification based on a spatial correlation random field requires the modeling of joint distributions of ground motion intensity measures at all interested sites. Therefore, the assessment of spatial correlation of ground motion is the first step to assess seismic loss at a regional scale. The quantity, type and distribution randomness and complexity of regional portfolio buildings have an important impact on pre-earthquake prediction and post-earthquake rapid assessment. This study introduces the basic theory for spatial correlation of seismic intensity parameters (IMs) using geo-statistics and the method for randomly generating a regional spatial correlation influence field using Monte Carlo simulation. A rapid loss assessment framework considering the randomness of spatial distribution of portfolio building structures is proposed. The framework uses “double-loop Monte Carlo random simulation” to simulate the spatial correlation influence field of ground motions and the spatial distribution of regional portfolio building structures, it realizes as a kind of rapid, efficient and accurate regional modeling and loss assessment. At last, taking 50 km ×50 km area as an example and, assuming that an earthquake event with Mw=7.2 occurred in the regional center, the direct economic losses of the earthquake with and without spatial correlation, fixed spatial distribution and random spatial distribution of regional building structures are calculated upon on the basis of different loss ratios. The results show that the loss ratio has an important influence on the accuracy of the assessment of the direct economic loss of regional earthquakes. Considering the spatial correlation, the Monte Carlo simulation statistics of the direct economic loss of regional portfolio building structures show a lognormal distribution, and the annual exceedance probability of the loss obtained by using Monte Carlo random simulation of the distribution of building structures is very close to the annual exceedance probability of fixed buildings on the whole. The annual exceedance probability of loss considering the spatial correlation of the ground motion influence field will be significantly greater than that of loss without considering the spatial correlation at the middle and high direct economic losses.