Objective To assess the safety and effectiveness of neonatal disease screening so as to provide basis for the establishment of a mechanism for managing neonatal disease screening. Methods Using the ideas of evidence-based medicine, a safety and effectiveness assessment of neonatal disease screening was made by means of literature induction. Results The techniques used in neonatal disease screening were highly safe, but their effectiveness was affected by a variety of links and factors. The differences reported in literature in such aspects as blood-collecting time, testing methods, cut-off values, and indexes for outcome evaluation might mean negative impact on the effectiveness. Conclusion More attention ought to be attached to the understanding and assessment of the safety of screening techniques and more efforts need to be made in conducting systematic studies into the effectiveness of screening techniques.