Objective To assess the effectiveness of multiple cleaning and disinfection interventions in the homes and kindergartens, in reducing gastrointestinal and respiratory illnesses of children.Methods From October 2010 to September 2011, we performed a prospective, controlled study in China.408 children under 5 years old were recruited and group randomized into intervention and control groups.Families and kindergartens in the intervention group were provided with antibacterial products for hand hygiene and surface cleaning or disinfection for one year.Control group followed usual hand hygiene and surface cleaning or disinfection practices.Each childs symptoms (fever, cough and expectoration, runny nose and nasal congestion, diarrhea, abdominal pain) and absenteeism due to illness were recorded every day.Results A total of 393 children completed the study, with similar baseline demographics in each of the 2 groups.Except for abdominal pain, the odds of symptoms (fever, cough and expectoration, runny nose and nasal congestion, diarrhea), illness (acute respiratory illness and gastrointestinal illness), and sick leave per person each month were significantly reduced by interventions.The rates of fever, diarrhea, acute respiratory illness, gastrointestinal illness and sick leave per person per year were significantly decreased as well.The protection rate was up to respectively 56.04% ([CI] 52.64% ~ 59.62%), 60.83% ([CI] 42.73% ~ 78.94%), 50.85% ([CI] 45.86% ~ 55.84%), 55.79% ([CI] 36.99% ~ 74.59%) and 37.75% ([CI] 24.14% ~ 51.37%).Conclusion Not only the acute respiratory and gastrointestinal illness but the sick leave rate in children were obviously reduced by multiple interventions.