Background: Human Papillomavirus (HPV) is a pervasive sexually transmitted infection implicated in various malignancies, notably cervical cancer. Despite the high disease burden in developing regions, knowledge gaps persist regarding HPV transmission, prevention, and associated diseases. Understanding patient awareness and perception is crucial for designing effective educational and preventive strategies. Methods: A cross-sectional study was conducted among outpatients attending the gynecology and medicine clinics of a tertiary care hospital in South India. A structured questionnaire was administered to assess sociodemographic information, awareness of HPV, familiarity with HPV-related conditions, and attitudes toward HPV vaccination. Data were analyzed using descriptive statistics and inferential tests to identify factors associated with awareness levels. Results: Out of 450 enrolled participants, 56% reported having heard of HPV, but detailed understanding was limited to 21%. A significant association was observed between higher educational status and greater HPV knowledge (p < 0.01). Only 28% of respondents were aware that HPV causes cervical cancer, and 19% recognized its connection with other anogenital malignancies. The majority (65%) expressed willingness to learn more about HPV prevention, although economic and cultural barriers were cited as potential obstacles to vaccination. Overall, gaps in accurate knowledge and risk perception emerged, underscoring the importance of targeted education and counseling. Conclusion: These findings highlight insufficient awareness of HPV and its associated diseases in a tertiary care setting in South India. Strengthening public health initiatives, prioritizing educational interventions, and increasing access to HPV vaccines can help bridge the knowledge gap, promote preventive behavior, and potentially reduce HPV-related disease burden.