Aiming at the problem of express freight scheme decision under multiple uncertain factors, the express freight scheme decision model and decision rule based on intuitionistic fuzzy rough set over two universes were proposed. Based on the intuitionistic fuzzy rough set theory over two universes, a fuzzy approximate space over two universes for express freight scheme decision was determined. The consumption degrees of fixed cost, transportation cost, transfer cost, carbon emission, transfer time and other transportation indices were regarded as intuitionistic fuzzy numbers, and the intuitionistic fuzzy relation between evaluation indices and transportation schemes were used to calculate the lower approximation set and upper approximation set, and the maximum intuitionistic index and Hamming closeness degree were introduced to determine the transportation scheme decision rules. Taking an express freight transportation line from Lanzhou to Beijing as the example, the optimal transportation scheme was selected from the 9 modes of transportation combined by road, ordinary speed railway and air according to the decision rules. Sensitivity analysis of transportation cost and transfer cost was performed to verify the accuracy of the results. The two optimal transportation schemes finally selected show the applicability of the intuitionistic fuzzy rough set over two universes on such problems.