Malaria was endemic in Hainan Island, China, for a lengthy period before its elimination. Here, we aim to gain a better understanding of malaria elimination by assessing and quantifying the relative effects of longitudinal changes in specific antimalarial interventions, socioeconomic development approaches, and malaria vectors on malaria prevalence in Hainan during the 1986-2009 pre-elimination period. Annual data were collected on the incidence of malaria, the number of residents protected by drugs (RPD), the number of residents protected by vector control, the presence of Anopheles minimus and Anopheles dirus, the annual per capita income of rural residents, major cash crop (rubber plantation) areas, the literacy rate of adult rural residents, and the rate of reinforced concrete house construction in rural areas. Backward stepwise multiple linear regression models were developed to identify the factors associated with the annual malaria incidence (AMI). The AMI declined from 20.3 to 0.8 per 10,000 population from 1986 to 2009; this decrease was significantly associated with an increase in the number of RPD and improved literacy rate among rural adults. The results of this study implied that the sustained distribution of antimalarial drugs and increase in education levels in risk areas significantly impacted the reduction and elimination of malaria infection in Hainan. We suggest that these findings could be applicable to malaria-endemic areas in Southeast Asia with similar natural and socioeconomic environments to Hainan and where malaria incidence has decreased to a low level.