Abstract Objective: To estimate the association between congenital syphilis and neonatal hearing screening failure in the state of Santa Catarina between 2017 and 2019. Methods: This is a cross-sectional, retrospective, analytical study with secondary data of neonates from the state of Santa Catarina born between January 2017 and December 2019. We used logistic regression analysis to estimate the association between the main exposure (congenital syphilis) and the study outcome (failure in the Neonatal Hearing Screening). Results: The study included 21,434 newborns evaluated in a Brazilian hearing health care service. A total of 351 (1.6%) newborns failed the Neonatal Hearing Screening, and 364 (1.7%) had congenital syphilis. In the adjusted analysis, newborns with congenital syphilis were 3.25 times as likely to fail the Neonatal Hearing Screening as neonates without this disease (95% CI: 2.01; 5.26). As for maternal age, the sample had a higher prevalence (53.5%) of mothers aged 20–29 years. Conclusion: There was an association between congenital syphilis and failure in Universal Neonatal Hearing Screening in the sample studied. There is a need for investments in public policies to value and strengthen the hearing screening program in the state to provide early diagnosis and intervention. Level of evidence: 5