Based on the matching data of China's manufacturing listed firms and prefecture-level cities from 2010 to 2018, the role of FDI technology spillovers, collaborative innovation and their interaction on manufacturing technology upgrading were empirically analyzed, and the heterogeneity under different enterprise ownership and industry types was further tested. It is found that FDI technology spillovers and inter-enterprise collaborative innovation can significantly promote manufacturing technology upgrading and form a positive interaction effect, while industry-university-research collaborative innovation has no significant effect on technology upgrading, and has not yet formed a synergy with FDI technology spillovers; in state-owned enterprises and technology-intensive industries, the interaction effect of FDI technology spillovers and inter-enterprise collaborative innovation is more significant.