The effect of culture and S T innovation is the result of common effort in knowledge chain of culture and S T integration. Culture and S T innovation team plays a core role on the realization of innovation resource sharing. Under the condition of moral hazard, short-term cooperation models can’t effectively motivate project leader to work together. Based on principal-agent theory, this paper designs long-term cooperation models of culture and S T innovation project under the condition of repeated game and proposes to establish expert database and reputation archives of culture and S T innovation workers for objective evaluating ability of culture and S T innovation workers. Through the analysis of the mathematical model, the author thinks that the reservation utility of project leader should be no less than the sum of discounted the reservation utility of short-term cooperation mode by innovation capacity and the expected revenue loss. The long-term cooperation mode achieves win-win results by balancing the profit between the parties and provides theoretical basis and advices for culture and S T integration activities of exploration and innovation.