Background: Female sex workers (FSWs) play an important role in transmitting Human Immunodeficiency Virus (HIV) and syphilis from high-risk groups to the general population. Syphilis and HIV infections are generally more prevalent among FSWs. However, in Ethiopia, up-to-date evidence about Syphilis-HIV co-infections among FSWs was lacking. Objective: To determine the magnitude and determinants of Syphilis-HIV co-infection among FSWs in Ethiopia, 2019-2020. Methods: A cross-sectional HIV and other sexually transmitted infections Bio-Behavioral Survey (HSBS) was conducted using respondent-driven sampling (RDS) among 6,085 FSWs in Ethiopia from August 2019 to January 2020. Data was collected, merged with laboratory data, and analyzed in R software using the RDS package. The odds ratio was calculated at 95% CI to measure associations between the dependent and independent variables. Variables that yield p<0.25 in univariate analysis were included in multivariate analysis. In multivariate analysis, variables with p<0.05 were declared as statistically significant. Results were presented in frequency tables and charts.