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Background: Malaria is one of the major human health problems that have become increasingly important in recent decades., Objective: The present study aimed to identify the epidemiological status of malaria in the years 2006-2018 in the southern region of Fars province in southern Iran., Methods: This is a cross-sectional descriptive-analytical study. The study population consisted of all persons with malaria referred to the Center for Disease Control in the four cities of Larestan, Gerash, Evaz and Khonj in the south of Fars province, Southern Iran, between 2006 and 2018. Frequency (%) was used to report descriptive statistics and mean and standard deviation for quantitative variables. The trend of malaria incidence during these years was analyzed using the Cochran Armitage Test. The significance level was considered 5%., Findings: A total of 190 cases of malaria in the period of 2006 to 2018 occurred in the southern region of Fars province; 77.9% were men, more than 95% were Afghans, and most of them were workers. The incidence of malaria in one hundred thousand people per month showed that most of the new malaria cases were in the months of July to October. The peak incidence was in August, with 19.88 cases per 100,000 people. Cochran-Armitage test results showed that this trend was not statistically significant (P = 0.399), despite an almost upward trend in malaria incidence in the south of Fars province., Conclusion: The results of this study showed that the trend of malaria in the south of Fars province was ascending; therefore, increasing surveillance activities to prevent and control malaria in such area is of utmost importance., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2020 The Author(s).)