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Background: A health-promoting lifestyle (HPL) can affect a person’s quality of life (QOL) and prevent many diseases. Objectives: The QOL and HPL of teachers and nurses are of great importance because of their influence on the community health and education of the new generation. The present study aimed to determine and compare the HPL and QOL of nurses and teachers in Zanjan, Iran in 2018. Methods: This descriptive, comparative, cross-sectional study was performed on 395 teachers of governmental schools, who were selected by cluster sampling, and 182 nurses, who were selected by census sampling. Data were collected using a demographic questionnaire, health-promoting lifestyle profile (HPLP II) questionnaire, and 36-item short-form health survey (SF-36) questionnaire. Data analysis was conducted in SPSS version 16 by measuring descriptive statistics (absolute and relative frequency, mean, and standard deviation) and inferential statistics (Kolmogorov-Smirnov test, Levene’s test, and independent t-test). Results: The results showed that most of the teachers were male (62.5%) and married (63.8%) with a bachelor’s degree (70.1%), while the majority of nurses were female (83%) and married (87.4%) with a bachelor’s degree (100%). Based on the findings, the HPL of nurses and teachers was rated as moderate (40.5% and 48.1%, respectively). Also, the QOL of nurses and teachers was at a moderate level (44.6% and 52.4%, respectively). Finally, the mean QOL and HPL were lower in nurses as compared to teachers (P