BACKGROUND: The Fourth National Oral Health Epidemiological Survey (FNOHES) reported an 89% caries prevalence among adults aged 35-44 in China. This study explored the current prevalence and determinants of dental caries in Guizhou Province, where socioeconomic conditions have changed. We aimed to identify factors influencing dental caries to inform future oral health policies and preventive strategies tailored to the region. METHOD: A total of 2,040 middle-aged adults from 11 districts and counties in Guizhou participated. Categorical variables were analyzed using chi-squared tests, and logistic regression identified key factors. Quantitative measures, such as the DMFT index, were used to assess the overall dental health of the participants. RESULT: The statistical analysis showed a caries prevalence of 79.6% and a mean DMFT of 3.11. Caries were more prevalent in urban areas and among females. Significant factors associated with caries included gender, residence, ethnicity, smoking status, toothpick use, dental visits, and self-rated oral health. CONCLUSION: The prevalence of dental caries remains globally high, as reflected in both developing and developed countries. Targeted interventions, particularly for females, urban residents, and ethnic minorities, are recommended. Public health initiatives should prioritize promoting safer oral hygiene practices and smoking cessation programs, including education on managing post-cessation cravings for sugary foods. Further research, including longitudinal studies, is needed to evaluate intervention effectiveness.