Existing studies have neglected the impact of regional factors on the liability of foreignness, but the development of regional economy in many developing countries is very uneven. The different degrees and different ways of regional economic agglomeration also affect the liability of foreignness which foreign subsidiaries face in the host country. In the discussions about regional factors constraints, the impact of regional economic agglomeration on the liability of foreignness is an urgent issue that needs to be solved. On the basis of further relaxation of the regional factor homogeneity assumption, the regional factors are introduced into the theoretical framework as a constraint to build a more general and more appropriate explanation of the influence of regional economic agglomeration on the liability of foreignness, so as to enrich and perfect the research system of liability of foreignness.