Complex integrated circuits (ICs) have complex functions and various working modes, which have many factors affecting the performance of a single event effect. The single event effect performance of complex ICs is highly program-dependent and the single event sensitivity of a typical operating mode is generally used to represent the single event performance of the circuits. Traditional evaluation methods fail to consider the cross effects of multiple factors and the comprehensive effects of each factor on the single event soft error cross section. In order to solve this problem, a new quantitative study method of single event error cross section based on a generalized linear model for different test programs is proposed. The laser test data is divided into two groups: a training set and a validation set. The former is used for model construction and parameter estimation based on five methods, such as the generalized linear model and Ensemble, while the latter is used for quantitative evaluation and validation of a single event soft error cross section of the model. In terms of percentage error, the minimum mean estimation error on the validation set is 13.93%. Therefore, it has a high accuracy to evaluate the single event soft error cross section of circuits under different testing programs based on the generalized linear model, which provides a new idea for the evaluation of a single event effect on complex ICs.