Abstract: Objective To analyze the socio-behavioral factors related to malaria re-emergence in the north area along Huaihe River, Anhui province. Methods Field investigation was carried out in Xutan town of Mengcheng county in 2006. Dry blood samples on filter paper were collected from all reachable residents aged over 1 year for detecting antibody level by indirect fluorescent antibody test (IFAT). The questionnaire survey was performed among the residents aged over 10 years to analyze their awareness on the knowledge about malaria and its control, malaria history in the past 2 years, the use of bed nets/curtains, the behaviors of sleeping in open filed and medical seeking of those with fever. Results The sero-epidemiological survey indicated that with a titer1 ∶ 20 as the criterion, the average positive rate of IFAT among the residents was 5.1%, the positive geometric mean reciprocal titre (GMRT) was 21.49 and total GMRT was 10.40. The rate of medical seeking of the febrile patients was up to 82.8%, but they usually made medical seeking at 5.1 days after fever onset averagely. The awareness rate of the knowledge about malaria control was low (21.1%, 116/548),and the awareness of self protection was only 4%. The bed nets/curtains use rate was 38.9% and the rate of sleeping in open field was 26.8%. The radical cure rate among those with malaria history in non-transmission season was 33.3% (2/6) in 2004 and 12.0% (3/25) in 2005. Conclusion Low immunity, poor awareness of self-protection among the local people,their behavior of sleeping in open field and delayed diagnosis and treatment the malaria cases were closely related to the re-emergence of malaria in the north area along Huaihe River.