Regional integration improves the internal production condition and external business environment of the enterprises, reduces the production cost and transaction cost of the enterprises and further boosts the promotion of the enterprise performance by the paths such as resources sharing, market co-construction, industrial co-vitalization and policy negotiation and so on. Taking the Yangtze River Delta Urban Economic Coordination Commission as a quasi-natural experiment, based on the micro-data of manufacturing enterprises in Shanghai, Jiangsu, Zhejiang and Anhui from 1996 to 2013 in China industrial enterprise database, this paper uses PSM-DID method to test the impact of regional integration on enterprise performance. The results show that, as a whole, regional integration has a significantly, steadily and intensifyingly boosting effect on enterprise performance and has stronger predictive effect on the enterprises joined latterly. Regional integration has promoting effect on the enterprise performance in many industries but has unfavorable effect on the enterprise performance in few industries. The promoting effect of regional integration is more significant on the performance of the enterprises with bigger scale at the initial stage but is more significant on the performance of the enterprises with smaller scale at the late stage. The farer the distance between Shanghai and the city joining the Commission is, the weaker the policy effect of regional integration on enterprise performance is. While regional integration boosts enterprise performance, we should pay attention to the diversification and changes of the policy effect, try to balance the difference of the policy effect between different regions and different economic subjects, meanwhile, implement multi-layer regional integration strategy, and weaken the waning effect of city distance on regional integration policies.