: Sex and gender minorities (SGMs) include individuals who do not comply with sexual binarism and heteronormative standards. They represent a high-risk population for Human Papillomavirus (HPV) infection and potential target of an HPV vaccine offer. This study investigates SGMs' knowledge, awareness and vaccination attitude regarding HPV. : This is a cross-sectional, questionnaire-based study. The target population was represented by SGMs living in Italy and using social media platforms of SGM rights associations. The study questionnaire was based on the literature and disseminated via said associations' social media. It included items regarding knowledge and awareness, expressed as seven-point Likert scales, and questions about personal information, sexual anamnesis and vaccination attitude. Data collection started on 1 November 2023 and ended on 8 December 2023. : The questionnaire was answered by 177 people. Knowledge and awareness scores were generally high (45.98 ± 6.14 and 34.21 ± 4.62, respectively). Regarding attitude, 31.64% of participants reported being hesitant or refusing HPV vaccination, mainly due to prohibitive costs or low perception of the vaccine's utility. Higher education was associated with a higher knowledge score (coeff.: 2.25; 95%CI: 0.69-3.82); likewise, a history of HPV-related lesions positively influenced the score (coeff.: 2.47; 95%CI: 0.20-4.75). The awareness score was only increased by a greater number of sexual partners (coeff.: 0.06; 95%CI: 0.01-0.11). Older age was proven to significantly increase the odd of vaccine hesitancy (OR: 1.07; 95%CI: 1.02-1.12). : Despite a good level of knowledge and awareness, the study population manifested significant barriers to vaccination. The main ones were related to the vaccine's cost and lack of medical information. Future efforts should focus on reinforcing vaccine offers to SGMs.