According to the brittleness theory of complex system, the brittleness risk’s internal cause of a project portfolio is proved to be the interactive coupling structure constructed by interaction effects among projects. The purpose of this research is to assess the brittleness risk of a project portfolio with a certain interactive coupling structure and present appropriate measures to control the brittleness risk. The brittleness risk’s measure process of project portfolio is dissected from the top down based on the quantitative analysis of interaction effects. Through calculating the probability and entropy of brittle link between projects, the brittleness safety grade is rated for all project relations composed by interaction effects. According to the rating result, the interaction effects of resource and outcome are the key internal causes of the brittleness risk of project portfolio. Finally, some measures are presented to control the brittleness risk of a project portfolio according to the brittleness assessment results and the brittle entropy change theory.