Abstract: Knowledge spillover is a manifestation of knowledge externality, its negative impact on Industry-University-Research Institute collaborative innovation can not be ignored. However, due to the ambiguity of knowledge spillover and the difficulty of measuring risk, it limits the in-depth application of econometric methods in this field, and should try to study from another perspective. The paper designs the independent variables based on the key influencing factors of knowledge spillover risks and builds a collaborative innovation knowledge spillover risk characterization function based on Cobb-Douglas model. Attempts to verify and analyze the theoretical logic of the minimum value and stability of knowledge spillover risks. The results show: The minimum value of collaborative innovation knowledge spillover risks exists within the controllable scope of the alliance, and decreases with the improvement of core organization knowledge innovation ability and alliance spillover knowledge quality; Under the premise that the risk reaches a minimum value, the possibility of rebound is positively correlated with the severity of environmental changes inside and outside the alliance; In addition, the risk stability has a negative correlation with the informal communication density between organizations and the rationality of organizational structure. Finally, based on the analysis result, constructing management framework of knowledge spillover risks of Industry-University-Research Institute collaboration innovation.