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Introduction: Youth smoking is a public health issue. However, the extent of smoking among young people, particularly among high school students, remains little known in Guinea. Objective: The objective of this study was to determine the prevalence and predictive factors of tobacco consumption in a high school in the Middle Guinea region in 2019. Study methods: This was a cross-sectional study with analytical aims, focusing on 353 high school students selected from the high school of Mali-center. A questionnaire adapted from the standardized questionnaire validated by the WHO and the CDC as part of the global student health surveys was used for data collection in November 2019. Logistic regression was used to identify predictive factors. Results: The prevalence of smoking was 9.92% [95% CI: 6.80-13.00]. Note that 76.20% of respondents did not know of any harmful effects of tobacco on health. Male sex [OR = 5.60 (95% CI: 3.25-7.15)], alcohol consumption by the student [OR = 12.94 (95% CI: 10.32-15.78)] and smoking by close friends [OR = 5.40 (95% CI: 3.77-7.49)] were the predictors of tobacco use. Conclusion: The prevalence of smoking and the ignorance of the effects of tobacco on health among high school students in central Mali should draw the attention of actors. Interventions based on education for personal development, youth entrepreneurship and tobacco legislation should be undertaken.