This paper empirically analyzes the impact of rural labor price changes on grain production and its regional differences. The results show that the rural labor price has a significant negative impact on the grain planting area and its proportion, which has an adverse impact on grain production; but it is relatively easy to mechanize. In the plains, the adverse effects of rising rural labor prices on grain production will be weakened. The results of the sub-regional study show that the increase in rural labor prices lead to a reduction in the area planted with grain in the northeast, central and western regions of China, but don’t have significant impact on grain production in the eastern region. Therefore, in the process of rising labor prices in rural China, in addition to focusing on food security and grain production issues, we should also pay attention to the impact of rural labor price increases on different regions, and take targeted measures to stabilize grain supply and ensure food security.