Cross-strait university students' entrepreneurship cooperation and exchanges have become increasingly frequent. However, What are the differences of potential entrepreneurs' entrepreneurial self-efficacy (ESE) and entrepreneurial intention(EI) and the impact mechanism of ESE on EI between the Mainland and Taiwan region has remained unknown. This empirical research based on 774 valid samples from 4 universities across the Taiwan Straits will reveal it. First of all, six-dimension scale structure of ESE for cross-strait college students is built. Then ESE and EI of college students on both sides are compared. Finally this study further investigates the impact of ESE on EI on both sides and its regional difference. The results show that there is no significant difference generally on ESE between the Mainland and Taiwan region college students except that entrepreneurial opportunity recognition self-efficacy of the Mainland college students is significantly higher than that in Taiwan region on dimension level, and the EI of college students in Taiwan region is significantly higher than that in the Mainland, and ESE of college student on both sides can positively predict EI and the main impact makes no regional difference.