Due to the influence of project portfolio risks, project portfolios can not effectively support the realization of enterprise strategies. Therefore, enterprises need to adopt appropriate risk response strategies to ensure the project portfolio success, but there are few methods to select project portfolio risk response strategies at present. Based on this, the paper firstly analyzes and measures the interference degree of risks to the implementation of strategies by combining the information entropy and the spherical fuzzy set(SFS). Secondly, the stochastic approach for link-structure analysis(SALSA) and the decision-making trial and evaluation laboratory(DEMATEL) are used to analyze and measure the correlation strength between the two-layer risks in a project portfolio. Then, according to the above process, the weights of risks are determined, and a decision model of project portfolio risk response is established based on the portfolio mental accounts and the regret theory. Finally, the effectiveness and practicability of the method are verified by a case study. The results show that 1) Both the risk interference to strategy realization and the correlation between risks have an impact on the selection of risk response strategies. 2) The influence of the change of risk to strategy realization interference weight on risk response decision is related to response budget. 3) The decision makers who pay less attention to the interference of risk on strategy realization tend to select the strategy set which can deal with the stronger correlated risks more; The decision makers who focus on the interference of risk to strategy realization tend to select the strategy set which can deal with the risks at the project portfolio level more.