This cross-sectional survey study aimed to assess the attitudes and knowledge of children’s guardians in Poland towards tick-borne encephalitis (TBE) and its vaccine, as well as to compare these attitudes to those regarding other infectious diseases and their vaccines. Data were collected through anonymous questionnaires, both paper-based and online, from 3030 respondents across Poland, with the majority being from TBE-endemic areas. The survey included questions on demographic characteristics, general vaccination beliefs, and specific perceptions of TBE and its vaccine. Statistical analysis revealed significant associations between willingness to vaccinate against TBE and factors such as general vaccination attitudes, information sources, vaccine safety ratings, and perceptions of disease severity. Results indicated that guardians from larger cities and those with fewer children were more likely to vaccinate. Additionally, parents who supported general vaccinations were significantly more willing to vaccinate against TBE. The study concludes that enhancing public awareness about the safety and importance of the TBE vaccine, especially in endemic regions, is crucial for improving vaccination rates. Targeted public health interventions addressing misconceptions and providing accurate information are essential strategies to increase TBE vaccine uptake and protect children from this serious disease.