Background: Hepatitis B virus (HBV) is a blood-borne infectious disease. Patients with hepatitis B may feel like influenza and might, in other cases, be asymptomatic, but blood analysis can detect the disease. Hepatitis B usually starts to cure on its own after a few months, but the disease can turn into chronic hepatitis if the virus is not cured and usually lasts a lifetime. Objective: this study aimed to estimate the knowledge, attitude and practice about hepatitis B virus and its vaccine among health science college's students of Jazan University, KSA. Methodology: thiscross-sectional study conducted targeting health sciences students of Jazan University in 2017. Data were collected using self-administered questionnaire which has been distributed among 400 students using stratified random sampling technique, the self-administration questioner aimed to estimate knowledge practice and attitude towards HBV and its vaccination and whether the students were vaccinated or not.  Analysis has been done by using computer program (SPSS) for displaying frequency, mean and percentage. Descriptive statistics and correlation analysis have been used to detect the association. Results: this study found that overall knowledge about HBV hazards and prevention among students was good and satisfactory (90.6%). The majority of the respondents (73.1%) had positive attitude toward HBV and its vaccine, 58.5% had poor practice, 63.3% received vaccination and only 39.2% were fully vaccinated. Conclusion: Medical and health sciences students were at high risk of exposure to the HBV by direct contact with patients and their body fluids or accidental injury by needles, that's why students should be vaccinated upon entry to colleges or before starting clinical training and well-educated about post-exposure prophylaxis when exposed to these injuries.