Background: The burden of cancer has been increasing among the young population worldwide, specifically in Saudi Arabia. The present study aims to assess the knowledge of cancer and its determinants and barriers to seeking medical help among university students. Methods: It is a cross-sectional study, and 300 students were selected through stratified random sampling. A validated and structured questionnaire was used. Descriptive statistics were used to calculate the mean and standard deviation of the variable. Regression analysis was used to determine the association of risk factors with the outcome variable of knowledge level. A P-value< 0.05 was considered significant. Results: Out of 300 study participants, most had inappropriate knowledge (67.7%). The important determinant which caused barrier to seeking medical advice is fear of being diagnosed positive cancer test. In univariate analysis, social science students whose father's occupation was a job were significantly associated (OR 3.27, CI 1.96-5.45, p-value 0.00) and (OR 1.70, CI 1.01-2.84, p-value 0.043) with in-appropriate knowledge. After adjusting covariates, the age group 16-21 years and social science students were significantly associated (OR 3.33, CI 1.22-9.10, p-value 0.019) and (OR 2.78,CI 1.58-4.90, p-value 0.000) with inappropriate knowledge towards cancer respectively. Conclusions: The study found that university students, specifically in the social science program, had inappropriate knowledge of cancer signs and symptoms. Health promotion programme should be developed to the young population of the society, it will help to prevention of the Cancer.