Background: The evidence showed that prostate cancer (PC) is the second most common malignancy in men globally. Unfortunately, it rarely produces symptoms, and the diagnosis is delayed until the tumor is advanced. Objectives: To determine the participants' uptake of prostate cancer screening (PCS). Also, to assess their perceptions regarding PCS. Furthermore, to evaluate the association between patients' knowledge of PC and their beliefs and behaviors towards PCS. Methods: This cross-sectional study recruited men aged older than 40attending the King Khalid University Hospital (KKUH) between October 2020 and March 2021. SMS messages were sent to a random sample of 228 participants, inviting them to participate in an online self-administered questionnaire. The questionnaire consisted of 1- demography and history of PCS; 2- the knowledge questionnaire about PC; 3-the Champion's Health Belief Model (HBM). Results: Out of the 228 participants, 45.2% were men aged 60 years and above, 54.4% with college degrees and postgraduate studies, and 92.5% were married. The median knowledge score was 5, and the range was 12. Most men (72.4%) had a low knowledge score, and 79.4% of them did not have a previous PCS. Men aged 60 + were more likely to undergo the screening than their counterparts, with P values of 0.005. Higher knowledge scores were associated with the perceived benefits of prostate-specific antigen (PSA), digital rectal examination (DRE), and health motivation, P values of 0.0001, 0.0001, and 0.02, respectively. PSA and DRE>s perceived barriers were associated with low knowledge scores, P values of 0.0001 and 0.003, respectively. A higher probability of PCS participation was associated with the older age group, a P value of 0.001. Low participation was associated with perceived barriers of DRE, a P value of 0.031. Conclusion: The majority of the participants had poor knowledge regarding PC and PCS. Only a fifth of the men did PCS. High knowledge was associated with PSA and DRE perceived benefits and health motivation.