Anti-HEV IgM is a diagnostic for recent or ongoing HEV infection. However, some patients with acute hepatitis E (AHE) negative for anti-HEV IgM in acute period were often observed in clinical practice. In this study, we constructed the anti-HEV IgA indirect ELISA assay to evaluate the significance of anti-HEV IgA. The specificity of anti-HEV IgA was 99.6%. Among 245 AHE patients, 84 samples from 84 patients were positive for HEV RNA. The positive rate of anti-HEV IgA, anti-HEV IgM and anti-HEV IgG in 84 samples positive for HEV RNA was 96.3, 97.6, and 88.1%, respectively, and no sample was negative for anti-HEV IgA and anti-HEV IgM simultaneously. Among 245 AHE patients, we found nine samples collected from nine patients in acute period were negative for anti-HEV IgM but positive for anti-HEV IgA and two samples were positive for HEV RNA. Detection of anti-HEV IgA can be a useful supplement for diagnosis of acute HEV infection especially in patients negative for anti-HEV IgM.