© 2021 Elsevier Inc.Purpose: The research was conducted to determine the hand hygiene and mask-wearing behaviors and related factors of secondary school students in the COVID-19 pandemic process. Design and methods: This descriptive cross-sectional study was conducted between March 02–April 022021 with 1284 students who continued their secondary education in a province in the east of Turkey. The data were collected face-to-face through the Descriptive Characteristics Form, the Mask-Wearing Behavior Form, and the Hand Hygiene Behavior Form. Percentage, mean, t-test in independent groups, Mann Whitney U test and Multiple Regression analysis were used in the evaluation of the data. Ethical principles were observed at all stages of the study. Results: It was determined that 80.1% of the students used disposable medical masks, 62.1% of their parents chose a mask suitable for the age of the student, and 52.1% used the mask they wore all day long. It was found that 41.4% of the students washed their hands before wearing a mask, and 51.9% after wearing a mask. It was determined that there was a significant relationship between students' mask-wearing behavior and gender, and hand hygiene behavior and gender, grade level, previous training on hand-washing and mask-wearing. As a result of multiple regression analysis, it was found that gender and mother's occupation had a statistically significant effect on mask-wearing behavior, while gender and previous training on mask-wearing had a statistically significant effect on hand-washing behavior. Conclusions/practice implications: Students exhibited correct behaviors regarding hand hygiene and mask-wearing, but some misbehaviors suggest that training is necessary, especially in the COVID-19 pandemic period.