Background: The double burden of communicable and noncommunicable diseases (NCD) is an increasing trend in low- and-middle income developing countries. Rural and minority populations are underserved and likely to be affected severely by these burdens. Knowledge among young people could provide immunity to such diseases within a community in the long term. In this study we aimed to assess the knowledge of several highly prevalent NCDs (diabetes, hypertension, and chronic obstructive pulmonary disease [COPD]) and several highly incident communicable diseases (malaria and diarrheal diseases) among Karen high school students in a rural district in far northwest of Thailand. The aim of the study is to explore information for devising life-course health education that will be strategically based in schools., Method: A cross-sectional survey approved by the ethics committee of Boromarajonani College of Nursing Nakhon Lampang (BCNLP), Lampang, Thailand was conducted in Thasongyang, Tak province, from September 2011 to January 2012. Questionnaires for assessing knowledge regarding diabetes, hypertension, COPD, malaria, and diarrheal diseases were delivered to all 457 Karen high school students attending Thasongyang high school. A total of 371 students returned the questionnaires. Experts' validation and split-half reliability assessment was applied to the instrument., Results: Students' main sources of health information were their teachers (62%), health care workers (60%), television (59%), and parents (54%). Familial risk factors of diabetes and hypertension were not known to more than two thirds of the students. Except obesity and physical inactivity, lifestyle-related risk factors were also not known to the students. Though living in a malaria-endemic area, many of the Karen students had poor knowledge about preventive behaviors. Half of the students could not give a correct answer about the malaria and hygienic practice, which might normally be traditionally relayed messages., Conclusion: Health education and knowledge about common NCD and communicable diseases are yet to be prompted among the Karen students. A broader and more comprehensive school-based health education strategy for prevention of double burden diseases would benefit the rural minority population at the Thai-Myanmar border.