The paper analyses the innovation efficiency of the Yangtze River Delta region （YRD） from 1995 to 2016，and defines the test model of industrial structure influence factors. The empirical results show that both new knowledge production in the region and foreign direct investment can promote the industrial structure of YRD upgrading，however，excessive knowledge stock within the region can impede the industrial structure upgrading because of path-dependence. Science and technology system mechanism，openness and cooperation，platform construction are put forward to upgrade the industrial structure of YRD.