Abstract: Objective The aim of the study was to explore whether plasma secreted amyloid precursor protein alpha (sAPP-α) can become a possible peripheral biomarker in the diagnosis of autism. asMethods A sensitive enzyme-linked immunosorbent assay (ELISA) method was used to detect plasma sAPP-α and brain derived neurotrophic factor (BDNF) in 205 children with autism and healthy children. Independent samples t-test and multiple regression were used to analyze the impact factors of sAPP-α.Results There was statistically significant difference in levels of sAPP-α between autistic children and healthy children (P< 0.001). There was increased expression of sAPP-α in autistic children. In addition, in a subset of children with severe autism, plasma level of sAPP-αwas significantly higher than children with mild-to-moderate autism. However, there was no difference in BDNF between the children with severe autism and children with mild-to-moderate autism. There was a significant positive correlation between sAPP-α level and the parental childbearing age, and negative correlations between sAPP-α and birth weight, as well as between sAPP-α and gestational weeks. Additionally, increased sAPP-α was found in premature, neonatal hyperbilirubinemia and neonatal hypoxic ischemic encephalopathy (P< 0.05).Conclusion Our findings support the use of sAPP-α as an accurate and sensitive laboratory parameter for early screening of autism spectrum disorders (ASD). Elder maternal age at childbearing, low birth weight, premature, neonatal hyperbilirubinemia and neonatal hypoxic ischemic encephalopathy may be responsible to the increase of sAPP-α.