Objective This study aimed to investigate adult tooth loss and its influencing factors in Huishui County, Qiannan Prefecture, Guizhou Province, where Buyi and Miao ethnic groups gather, identify risk factors, and carry out early prevention and treatment of tooth loss to reduce the risk of disease. Methods A multi-stage stratified random sampling method was used to select 4 216 adults in the Huishui area where the Buyi and Miao ethnic groups gather. Their oral missing teeth were examined, and a questionnaire survey was conducted. Statistical analysis was conducted on the survey results using single-factor, multi-factor Tamhane’s T2, and multi-factor Logistic regression analysis. Results A total of 4 216 people were surveyed, including 1 594 males and 2 622 females, with an age range of 18-93 years and an average age of 50.5 years. A total of 7 214 teeth were missing, with a missing tooth ratio of 31.45% and an average of 1.7 missing teeth per person. The denture restoration rate for missing teeth is 32%. Single-factor analysis showed that age, ethnic group, educational background, occupation, family monthly income, smoking, length and frequency of tooth brushing, drinking, length and frequency of exercise, watching electronic products, acid, numbness, spicy and light diet, diabetes, hypertension, and heart disease had an impact on tooth loss. Multi-factor analysis showed that residents of the Miao ethnic group, those with high school or university education, and those with a monthly income of over 8 000 yuan are negatively correlated with tooth loss; being over 80 years old, farming, smoking for more than 40 cigarettes per day, smoking for more than 20 years, ne-ver brushing teeth, brushing for less than 1 min each time, drinking every day, watching electronic products for less than 2 h per day, never participating in exercise, doing outdoor exercise for more than 4 h per day, diabetes, hypertension, and heart disease are factors for having more serious tooth loss. Multi-factor Logistic regression analysis showed that age, occupation, highest educational level, monthly family income, brushing time, alcohol consumption, exercise time, weekly exercise frequency, daily viewing time for electronic products acidity, lightness, and hypertension are important influen-cing factors for tooth loss. Conclusion Residents in Huishui County, Guizhou Province, have a high incidence of tooth loss and a generally low rate of denture restoration. Efforts should be made to address the important influencing factors of tooth loss and increase the control of tooth loss diseases in this area.