Accumulation of β‐amyloid protein (Aβ) is one of the most important pathological features of Alzheimer’s disease. Although Aβ induces neurodegeneration in the cortex and hippocampus through several molecular mechanisms, few studies have evaluated the modulation of transcription factors during Aβ‐induced neurotoxicity. Therefore, in this study, we investigated the transcriptional activity of transcription factor CP2 in neuronal damage mediated by Aβ (Aβ1–42 and Aβ25–35). An unbiased motif search of the transferrin promoter region showed that CP2 binds to the transferrin promoter, an iron‐regulating protein, and regulates transferrin transcription. Ectopic expression of CP2 led to increased transferrin expression at both the mRNA and protein levels, whereas knockdown of CP2 down‐regulated transferrin mRNA and protein expression. Moreover, CP2 trans‐activated transcription of a transferrin reporter gene. An electrophoretic mobility shift assay and a chromatin immunoprecipitation assay showed that CP2 binds to the transferrin promoter region. Furthermore, the binding affinity of CP2 to the transferrin promoter was regulated by Aβ, as Aβ (Aβ1–42 and Aβ25–35) markedly increased the binding affinity of CP2 for the transferrin promoter. Taken together, these results suggest that CP2 contributes to the pathogenesis of Alzheimer’s disease by inducing transferrin expression via up‐regulating its transcription.