Opisthorchiasis is a major problem in Thailand particularly in northeast region which also has a high incidence of cholangiocarcinomas. Since health modification is needed, this quasi-experimental study aimed to assess the effectiveness of a health education program based on self-efficacy and social support in Tha Tum district, Surin province, Thailand. A total of 70 participants were purposive selected with a history of opisthorchiasis. Participants were divided into experimental and control groups, each with 35 subjects. The experimental group received a health education program composed of: (1) knowledge improvement, lectured with multimedia, demonstration, brochure, and handbook; (2) group discussion about their health beliefs, sharing their ideas and experience; and (3) social support from village health volunteers (VHV), heads of villages (HV), friends, and members of families, and public health officer (PHO). Follow-up was by PHO/VHV/HV, with provision of certificates and flasg for household that did not eat raw fish. Data were collected by predesigned questionnaires after implementation of the program for 3 months. Comparative data was analyzed by paired simple t-test and independent t-test. The results revealed that the experimental group had mean score of knowledge higher more than before the experiment (mean difference=3.1, t=3.915, 95%CI-3.3, -1.8 p-value=0.001), and the control group (mean difference=2.5, t=4.196, 95%CI=1.4, 3.6, p-value=0.001) with statistical significance. The mean scores of practice were higher than before the experiment (mean difference=4.6, t=4.331, 95%CI-5.3, -3.1, p-value=0.001), and control group (mean difference=4.4, t=6.142, 95%CI=4.2, 7.9, p-value=0.001). The mean scores of perceived susceptibility and perceived severity of opisthorchiasis, al well as perceived benefits and perceived barriers to prevention of opisthorchiasis, were also higher than before the experiment and in the control group (p-value <0.001). In conclusion, this was a successful health education program for liver fluke avoidance. Therefore, it may useful for further behavior modification in the other epidemic areas.