Abstract: Regional diversification development plays an important role in enhancing productivity, promoting employment and stabilizing the economy. Regional industrial change is largely understood by evolutionary economic geographers as an endogenous phenomenon so far and the role of external resources in regional diversification development has been neglected. Actually trans-regional cooperation innovation is one of the important ways to obtain external knowledge in the region. Although many studies have confirmed the positive impact of extraregional knowledge inputs on innovation, the impact of these innovations on regional industrial continuity and change is rarely mentioned. Using the invention patent data of 41 cities from 2000 to 2017, this study measures the diversification level and cooperative innovation in the Yangtze River Delta which has a significant regional economic integration characteristics, and empirically tests the role of intra-regional and inter-regional cooperative innovation in the process of regional diversification. The results show that: (1) The level of related and unrelated variety of cities in Yangtze River Delta generally increases gradually and tends to be stable, With the development of economy, the diversity of cities is gradually narrowing; (2) Cooperation innovation is an important carrier of knowledge flow. Out-of-area cooperation patents are dominated in the Yangtze River Delta region, that is the proportion of participants in the city of cooperation patents is generally smaller than that of participants in other cities, while participants outside the city are mainly located in the Yangtze River Delta region. Cooperative innovation contributes to the development of related variety in Yangtze River Delta, but has no significant impact on unrelated variety; (3) The number of participating teams in cooperative innovation has no significant relationship with regional related and unrelated variety; (4) The higher the proportion of inter-regional cooperation in cooperative innovation, the more related and unrelated variety can be promoted. That is innovation in non-local knowledge source activities can promote regional related and unrelated variety. Therefore, in the process of promoting the diversification of regional industries, attention should be paid to strengthening the cooperation between regions and guide the development of regional industries with the help of external forces.