Inspired by the activation mechanism of slow anion channels 1 (SLAC1) in plants that proton pump reversibly induces plant stomata open for CO2 adsorption, a CO2-switching H+ conduction/HCO3− diffusion dual ion channel (CO2-switching-DIC) was constructed by assembling γ-cyclodextrin-MOF (γ-CD-MOF) and 3,4,9,10-perylenetetracarboxylic acid (PTCA) for CO2 chemiresistive sensing. The obtained CO2 sensor exhibited high response (Rg/R0 = 1.33, 50 ppm) and selectivity, low practical limit of detection (1 ppm) and excellent consistency (94.5%) with a commercial infrared CO2 meter at room temperature. It is indicated that hydrogen bond networks in CO2-switching-DIC will be enlarged with the increasing of carboxylic group’s content on perylene skeleton, thereby modulating proton conductivity at molecular level and furthermore CO2 sensing performance of the composite. The CO2-switching-DIC-based sensor has been utilized to distinguish the exhaled CO2 concentration between lung cancer patients and healthy individuals, illustrating its promising application prospect in non-invasive diagnose.