Back Ground: Human immune deficiency virus was a worldwide pandemic, yet there is no proven medicine and vaccine to cure or prevent it. Prevention is only the mainstay solution to control the spread of the virus among high-risk young populations. Young peoples were at the greatest risk of HIV because of several influencing factors like: maturity-related physiological, emotional changes, sexuality, peer pressure, economical problem, and knowledge gaps concerning HIV. Therefore, continuously assessing prevention practice towards HIV among vulnerable young populations is relevant to yield necessary intervention.Methods and materials: Health care facility-based cross-sectional study design took place from December 01/2020 To January 01/2021. The multistage sampling technique was used in this study and a total of 615 participants were enrolled in the study. A self-administered questionnaire technique was employed to collect the data. The data was cross-checked before entered into Epi-Data version 4.4.3.1 and exported to SPSS Statistics Version 25 for analysis. Descriptive and inferential statistics were needed in the study. Bivariate logistic regression was done to check the association between dependent and independent variables. Variables that had association at p< 0.25 were entered into a multivariate logistic regression model to obtain an adjusted odds ratio. Statically significance cut point settled at p < 0.05 with 95% confidence intervals. Results: Out of the 615 students, 586 were completed the questionnaires in which 95.3% of respondents rate. The overall scores of poor knowledge, unfavorable attitude, and unsafe practice concerning HIV in the current study were 25.1%, 27.5%, and 24.2%. Of all study subjects; 38.7% were undifferentiated HIV from AIDS and 20.1% of them were wrongly reported as HIV/AIDS was a curable disease. Slightly more than half 51.5%, 28.2%, and 19.3% of the respondents were misbelieved that HIV transmitted by mosquito bit, eating food cooked by HIV positive person, and handshaking respectively. Voluntarily counseling and testing service was not utilized by (34.8%) respondents and 139(23.7%) were sexually active. Early initiation of sex at age < 15 years old was reported by 70(50.4%) and the mean of first sex was (15.68 + 2.13SD). Females were 71.6% time more likely protect from HIV AOR = 0.284, 95% CI = 0.18-0.43), Age group 15-19 (AOR = 4.69, 95%CI =2.33-9.42), singles in marital status (AOR= 7.03, 95%CI =3.19-15.52), Visiting sexual related video (AOR= 0.202, 95CI = 0.11-0.38) and sharing sharp (AOR= 0.089, 95%CI = 0.04-1.21) were factors significantly associated with practice towards HIV. Conclusion: Misconception on ways of HIV transmission and misbelieves towards people living with HIV, Knowledge, and practice gap were identified in this study. HIV risk behavior such as drinking alcohol, vising sexual-related videos, sharing sharp materials practiced by some of the study participants. Therefore, continuous and age-appropriate youth-friendly health services emphasized risk behavior reduction and delay in early initiation of sexual intercourse must be given to youth. Furthermore, training focused on HIV, ways of transmission, and how to prevent it must be given by the concerned bodies to step up the students’ knowledge, attitude and practice. Additionally, all stakeholders including health care institutions, education institutions, and mass-medias give strong concern to alleviate misconceptions around HIV/AIDS particularly in this time of the COVID-19 pandemic.