This study aimed to assess baseline knowledge, attitudes, and practices about severe fever with thrombocytopenia syndrome (SFTS) and identify the target population for health education programs in endemic areas of Anhui, China. This cross-sectional study was conducted from May to June 2017. Of 752 participants, 383 (50.9%) were from Nanqiao District, 397 (52.8%) were female, and 430 (57.2%) were farmers; 37.4% had heard about SFTS, but knowledge of symptoms and signs including fever (34.2%), leukopenia (8.0%), and thrombocytopenia (10.1%) was low. Only 12.1% knew that SFTS virus is transmitted by ticks, 9.4% realized that the blood and body fluid of SFTS are infectious, and only 38.2% thought that the tick should be paralyzed using medical alcohol or iodine. Meanwhile, 61.3% wore long-sleeve clothes, whereas 20.2% used repellents. Median scores for knowledge, attitudes, and practices, and the total score were 4.0, 6.0, 5.0, and 16.0, respectively. Knowledge was influenced by region (OR = 0.632, 95% CI: 0.399-0.999), education (OR = 0.516, 95% CI: 0.434-0.612), gender (OR = 1.865, 95% CI: 1.165-2.987), and age (OR = 3.406, 95% CI: 2.345-4.947). Education was a predictor of lack of appreciation of infection risk (OR = 0.519, 95% CI: 0.449-0.599) and practice (OR = 0.481, 95% CI: 0.396-0.584). Our findings indicate that SFTS-related health education programs are required for females; participants from Qianshan Prefecture; those with an occupation of farmer, retiree, houseworker, or unemployed; elderly participants; and those with low education. Large-scale sustainable health education programs focusing on the target populations are urgently needed in endemic areas.