Background: Drying up of lakes is among the most important environmental disasters, which could have a great impact on human health. Since public perception is important in shaping behavior and policy-making, this study was conducted to evaluate the public perception about the health effects of Lake Urmia drying up. Methods: In this cross-sectional study, a questionnaire was prepared and validated in 4 phases, including content validity, construct validity, test-retest reliability, and internal consistency. The online version of the questionnaire was designed in the Google Forms section and shared among public groups to be completed. The printed version of the questionnaire was completed by 2 trained interviewers in 6 villages near Lake Urmia using the convenience sampling method. Data analysis was performed using univariate statistics, including the Mann-Whitney and Kruskal-Wallis tests, and multiple linear regression as multivariate statistics. Results: In total, 475 people completed the online and printed questionnaires, of whom 261 (54.9%) were men. The mean age (SD) of participants was 38.4 years (11.18). The mean (SD) of the overall perceived risk was 3.54 (1.28). For the group of socioeconomic determinants of health, the mean (SD) perceived risk was found to be 3.63 (1.19), while for the group of diseases, it was 3.45. (1.31). In the group of social determinants of health, migration with a mean (SD) of 3.76 (1.24) had the highest perceived risk, followed by income loss (3.63 [1.12]) and job loss (3.49 [1.20]). The highest mean (SD) perceived risk in the group of diseases belonged to lung diseases (3.99 [1.05]), hypertension (3.70 [1.17]), and cancer (3.68 [1.23]), respectively. Conclusion: The general public had a strong notion that the drying up of Lake Urmia posed health risks.