Influenza-Like Illness (ILI) sentinel surveillance was initiated by the Communicable Disease Control Department (CDC), Ministry of Health, Cambodia and its partners to evaluate the epidemiology of influenza and identify the circulating strains. The surveillance started in late 2006 in four sentinel sites. The objectives of this study were 1) to document the incidence of LI and confirmed influenza cases reported in the national surveillance system from 2006 to 2008, just after the system and the definition were revised, 2) to identify the strains of influenza virus, 3) to compare the major demographic and clinical characteristics between ILI patients having positive and negative tests for influenza virus. An ILI case was defined as having a fever of at least 38 degrees C (axillary), cough or sore throat. A total of 155,866 ILI cases were reported to the CDC from 4 sentinel sites in Cambodia from August 2006 to December 2008. Specimens were collected in 1.8%. Of these, 9.6% tested positive for influenza. Influenza was observed to occur mainly from August to December, with a clear seasonal peak in October, as shown in the data from 2008. A new case definition beginning in August 2008 resulted in a decrease in weekly RI reported cases (from an average of 1,474 cases to 54 cases) and the proportion of positive tests for influenza increased (5.3% vs 29.3%). Influenza and ILI are seasonal in Cambodia. A higher body temperature was used to define ILI, which improved the influenza positivity rates.