The food selection and processing stage are important stages to prevent food poisoning. A good level of knowledge and practice regarding food selection and processing among people who are responsible for the family meals are important. In this study, we aimed to investigate the knowledge and practice of primary food caregivers regarding food poisoning prevention in food selection and processing and identify the factors that influence these outcomes. The current study applied a cross-sectional study to investigate 422 primary food caregivers in urban areas in Vietnam. Data were collected using a structured questionnaire, and knowledge and practice were assessed based on pre-defined criteria. The data were analyzed using descriptive statistics, chi-square test, and logistic regression. Our study found that 78.9% of people had good knowledge regarding food poisoning prevention in food selection and processing. Furthermore, 84.4% of people had correct practice in this regard. Our study also revealed that household income level and educational level were associated with knowledge and practice, respectively. The proportion of correct practice was higher in the group with good knowledge (90.4%) compared to the remaining group (61.8%). The results indicated that the proportion of good knowledge and practice were high among food caregivers, but further efforts are needed to improve the knowledge and practice of food caregivers with lower household income and educational levels. The findings also emphasize the importance of communication campaigns to enhance knowledge related to food poisoning prevention.