Introduction: One of the most prevalent conditions affecting the vaginal organs is the human papilloma virus (HPV). Human papillomavirus (HPV) knowledge and attitudes have been the subject of numerous studies in Saudi Arabia. However, there are only a few studies that have examined university students’ attitudes and knowledge of the human papillomavirus and the vaccine that is associated with it. Aim: To predict the level of knowledge and attitudes regarding HPV and its related vaccine among undergraduate nursing students. Methodology: This was descriptive cross-sectional research. After being selected from Princess Nourah bint Abdulrahman University’s College of Nursing, 307 nursing students agreed to take part and completed an online survey that was self-administered. Results: The majority of the participants (73.5%) had a low level of knowledge of HPV with a mean score of 2.77 ± 1.78. In addition, more than half of the participating nursing students (57%) had a moderate attitude toward HPV vaccination with a mean score of 51.18 ± 11.16. The study results also verified that there was a highly significant correlation between the nursing students’ demographics and their knowledge and attitudes toward HPV (p< 0.001). According to the SEM, nursing students’ knowledge regarding HPV accounted for 48% of the variance in students’ attitudes. Conclusion: Nursing students’ knowledge regarding HPV vaccination is an important predictor of students’ attitudes regarding HPV.