Based on the panel data of 13 major grain producing areas in China from 2004 to 2021, this paper considers the fertilizer “zero growth” policy in 2015 as a quasi-natural experiment, and adopts regression discontinuity to empironally test the influence of the policy on the fertilizer application level in China’s major grain-producing areas, and then analyzes the influence of the policy on China’s food security. The regression discontinuity results showed that the fertilizer “zero-growth” policy can significantly reduce the fertilizer application intensity, and at the same time have a significant promoting effect on the grain yield and the yield increase of the three major grain crops (rice, wheat and corn). The mechanism analysis showed that the promotion effect of the fertilizer “zero growth” policy on grain output was due to the improvement of fertilizer utilization efficiency, and the highly concentrated and large-scale action of fertilizer reduction and efficiency increase in major grain producing areas could generate scale effect of grain increase. Heterogeneity analysis showed that under the impact of the fertilizer “zero growth” policy, the total grain yield and rice, wheat and corn yields in the eastern and central regions increased significantly, while the fertilizer application intensity in the central and northeast regions decreased significantly. While achieving fertilizer reduction and efficiency increase, the grain production capacity of the major grain producing areas has not decreased or even increased, thus effectively ensuring the national food security. This indicates that further implementation of the fertilizer “zero growth” policy can achieve a “win-win” of fertilizer reduction and efficiency increase and ensuring food security, better promote the green development of agriculture, and help build China into an agricultural powerhouse.