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Pituitary adenylate cyclase‐activating polypeptide (PACAP) receptor 1 (PAC1‐R) is the neuropeptide PACAP‐preferring receptor‐mediating neuroprotective activity. In order to clarify the biological mechanism of its expression, we cloned the 2,526 bp promoter fragment from −2,500 to +26 of the transcription initiation site of human ADCYAP1R1 gene and constructed the novel promotor reporter system named pYr‐PromDetect‐PAC1p. It was found in SH‐SY5Y cells low concentration (<10 nM) of hydrogen peroxide (H2O2) significantly promoted the activity of PAC1‐R promoter in dose‐dependent way, which was significantly inhibited by the transcription factor specificity protein 1 (SP1) inhibitor mithramycin A and was further confirmed in the deletion mutation of the predicted SP1 binding sites. Moreover, higher concentration of H2O2 (>10 nM) inhibited the activity of PAC1‐R in dose‐dependent way. The hormesis effect of H2O2 on PAC1‐R promoter would help to further clarify the physiological effect of low‐dose reactive oxygen on nervous system. Practical applications PAC1‐R mediates well‐known neuroprotective, neurotrophic, and neurogenesis effects, which is an important drug target for neurodegenerative diseases. The hormesis effects of oxidative stress on PAC1‐R expression not only help to explain the hormesis effects of oxidative stress on nerve system, but also offer a novel strategy to increase the expression of PAC1‐R for the nerve protection or nerve generation. For example, taking advantage of low degree of oxidative stress to increases the expression of PAC1‐R might help prevent subsequent surgical serious injury on the nervous system. The activation of PAC1‐R promoter by low concentration of H2O2 would help to further clarify the physiological effect of low‐dose reactive oxygen on nervous system.