It is urgently necessary to be aware of the distribution and risk areas of liver fluke, Opisthorchis viverrini,for proper allocation of prevention and control measures. This study aimed to investigate the human behavior,and environmental factors influencing the distribution in Surin Province of Thailand, and to build a modelusing stepwise multiple regression analysis with a geographic information system (GIS) on environment andclimate data. The relationship between the human behavior, attitudes (<50%; X111), environmental factors likepopulation density (148-169 pop/km2; X73), and land use as wetland (X64), were correlated with the liver flukedisease distribution at 0.000, 0.034, and 0.006 levels, respectively. Multiple regression analysis, by equationsOV= -0.599 + 0.005(population density (148-169 pop/km2); X73) + 0.040 (human attitude (<50%); X111) +0.022(land used (wetland; X64), was used to predict the distribution of liver fluke. OV is the patients of liver flukeinfection, R Square= 0.878, and, Adjust R Square= 0.849. By GIS analysis, we found Si Narong, Sangkha, PhanomDong Rak, Mueang Surin, Non Narai, Samrong Thap, Chumphon Buri, and Rattanaburi to have the highestdistributions in Surin province. In conclusion, the combination of GIS and statistical analysis can help simulatethe spatial distribution and risk areas of liver fluke, and thus may be an important tool for future planning ofprevention and control measures.