With the deepening of globalization, R&D cooperation with large foreign firms has gradually become an important way for domestic firms to participate in the innovation-driven development strategy. This paper analyzes the factors influencing the endogenous selection of international cooperative R&D of downstream firms by constructing the negotiation game model under the situation of intermediate trade. This paper finds that only when the R&D spillover effect is relatively small, the downstream firms will choose to conduct international R&D cooperation. However, if the R&D spillover effect is too small, the international cooperative R&D activities of downstream enterprises will lead to the decline of social welfare. We further found that the enhanced monopoly of the upstream market and the policy of final product trade liberalization would promote the international cooperative R&D behavior of enterprises in the downstream of the industrial chain.