The nerve inflammation induced by the interactions between Aβ1- 42 and microglia has been regarded as the important pathological indication of Alzheimer’s disease (AD). Acid-sensing ion channel (ASIC) involved in the inflammatory response and immune regulation of microglia. To observe the effects of the expression and electrophysiological properties of ASIC in microglia after exposure to Aβ1-42, primary cultured rat microglia were incubated with Aβ1-42. The protein expression and distribution of ASIC1, ASIC2a and ASIC3 were tested by Western blotting and immunofluorescence experiments. Whole-cell patch clamp was adopted to detect the ASIC current properties of microglia. Calcium imaging was performed to investigate the ion permeability of ASIC in microglia. The results showed that the protein expression of ASIC1 increased in Aβ1-42 stimulated microglia, the protein expression of ASIC1 in the cytoplasm and nucleus both increased. Meanwhile, acid-induced ASIC current and elevation of intracellular calcium increased, which could be inhibited by the nonspecific ASIC antagonist amiloride and specific ASIC1 blocker PcTx1. Therefore, this study confirmed that the functional expressed of ASIC1 increased in Aβ1-42 stimulated microglia, which make ASIC1 easily become activated by extracellular rapid acidification and produce more powerful inward current and acquire permeability to calcium ions, and thus affect the inflammatory response and immune regulation of microglia. This study provides valuable ideas and references for the further exploration of sensing pathway and response regulation of microglia and the occurrence of neurodegenerative diseases.