Colorectal cancer (CRC) is a significant public health issue, particularly in low- and middle-income countries like Thailand. While numerous studies advocate for regular screenings and health promotion programs to mitigate CRC risk, there is a notable lack of tailored health promotion models specifically designed for high-risk groups in Thailand. This research aims to develop a health promotion model to prevent CRC in high-risk groups through a quasi-experimental design. The study involved 68 Thai participants aged 40–70 years, divided equally into experimental and comparison groups. Independent-Samples t-test, Paired-Samples t-test, and one-way variance test (F-test) were employed to analyze the data. The comparison of baseline average scores for physical health, mental health, social health, and knowledge on health-promoting behaviors between the experimental and comparison groups revealed no significant differences. However, following the experiment, the average scores in physical health (t = −2.81, p = 0.01) and mental health (t = −10.30, p < 0.001) were significantly higher compared to pre-experiment levels, with the exception of social health (t = 0.07, p = 0.94). Furthermore, the average knowledge scores related to promoting physical, mental, and social health in the experimental group also showed a significant increase after the experiment (t = −4.53, p < 0.001). The findings suggest that health personnel should advocate for annual CRC screening and the implementation of health promotion programs, especially focusing on physical, mental, and social aspects for at-risk populations. This study underscores the need for long-term health promotion models to achieve continuous and sustainable health improvements in these groups.