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Background: Human immunodeficiency virus (HIV) and sexually transmitted infections (STIs) can cause severe and fatal complications; knowledge about these diseases is essential for promoting safe sex practices and modifying behaviours that are harmful to one's health. This study investigates Syrian people's understanding, attitudes, and behaviors towards HIV/AIDS and STIs, aiming to identify factors promoting safe sex practices and modifying harmful behaviors. Methods: This online cross-sectional study was conducted in Syria between 3 September and 23 November 2022, involving all 18+ individuals. The questionnaire was adapted from a previous study containing 74 questions from five sections: socio-demographic information, knowledge and practice regarding STIs, knowledge and practice regarding HIV/AIDS, attitude towards HIV/AIDS, and attitude regarding STIs and analyzed using descriptive and multivariate logistic regression. Results: The study involved 1073 participants mostly aged between 18-30, with 55.3% females. Over half had good awareness of STIs and HIV/AIDS, with 55% and 63% respectively. Specifically, the overall knowledge level of STI type, signs/symptoms, risks of transmission, preventive methods, and complications for untreated STIs were (45.7%), (52.9%), (58.1%), (66.1%), and (59.6%), respectively. Medical field respondents had higher knowledge of HIV (P-value < 0.05, OR = 2). Conclusion: Our results show that Syrian people have a knowledge level of STIs and HIV was moderate. However, the attitude toward STIs was negative, as less than half of the participants had a good attitude. It is essential to solve these knowledge gaps, especially in low-income countries such as Syria. [ABSTRACT FROM AUTHOR]