Background: This study aimed to evaluate the correlation between the presence of hairy tongue and H. pylori infection in patients referring to their blood test based on the serum levels of anti-H pylori IgG antibodies. Methods: This cross-sectional study was conducted in the Department of Oral Medicine, University of Damascus Dental School, between February 2021 and January 2022. The sample size of 40 patients (23 males, 17 females), whose ages ranged from 20–79 years with a mean age of 41.5 ± 12 years, was calculated using the G*power 3.1.3, with a statistical power of 80% and a significance level of 0.05. The hairy tongue index was assessed by a visual method based on observing the dorsum tongue appearance. Then, a blood test was performed to detect the presence of H. pylori by Immulite 2000 XPi. Statistical analysis was performed using SPSS software 22.0, Chi-square. Results: The prevalence of hairy tongue was higher among males (75%) as compared to females (25%) and was found to be statistically significant (p = 0.026). The hairy tongue lesions were found to be least in the 20–39 age group and most prevalent in the 40–59 age group, without statistically significant correlation. H. pylori infection was detected positive in 70% and negative in 30% of hairy tongue patients, compared to the control group, where the rates were 15% and 85%, respectively, with a statistically significant correlation between infection with H. pylori and hairy tongue (p = 0.001). Conclusion: Our results strongly suggest that the hairy tongue might be considered an indicator of H. pylori infection.