Distinct cropland acidification has been reported in China due to nitrogen (N) fertilizer overuse. However, the impacts on food production and thereby on food security are largely unknown. Yield losses in the period 1980–2050 were therefore assessed by simulating soil pH changes combined with derived pH-yield relationships for wheat, maize and rice. If the N fertilizer input continues to increase at 1% annually, the predicted average soil pH decline is about one unit and relative yield losses are expected to increase from approximately 4%–24% during 2010–2050. If the N fertilizer increase stops in 2020 (N2020), the expected losses are approximately 16% in 2050, which is comparable to a scenario of 100% crop residue return (100%RR). However, if 30% of the N fertilizer is replaced by manure N (30%MR), the losses reduce to near 5% in 2050. Soil acidification was predicted to reverse and expected losses are only 2.5% in 2050 in a combined scenario of N2020, 100%RR and 30%MR. Our results illustrate the potential food insecurity induced by cropland acidification and address the necessity of mitigation.