Objective To investigate the influential factors of Down's syndrome and to provide evidences for prevention. Methods A case-control study was conducted among children with or without Down's syndrome at Children's Hospital of Xuzhou,from January 2012 to December 2013.Parents of cases with Down's syndrome and controls were asked to fill in a questionnaire. Results Logistic analysis showed that Down's syndrome was associated with advanced maternal age(≥35 years old)(OR=5.55),maternal pre-pregnancy fever (OR=7.87),exposure to pesticides (OR=12.90),the surrounding environmental pollution (OR=6.94),decoration or purchasing new furniture or a new car (OR=6.85),maternal manicure (OR=44.58). Conclusions Down's syndrome is affected by multiple factors.Risk factors for Down's syndrome will include advanced maternal age(≥35 years old),maternal pre-pregnancy fever,exposure to pesticides,the surrounding environmental pollution,decoration or purchasing new furniture or a new car,maternal manicure.