Syphilis is a sexually transmitted infection (STI) that is a global problem. According to WHO, syphilis is still high, reaching 5.6 million cases of syphilis worldwide in adolescents and adults (age 15-49 years). WHO estimates that every year there are approximately 350 million new sufferers of STIs in developing countries, including Indonesia; the prevalence of syphilis occupies the second place of all types of STIs, namely syphilis by (21.7%). This study aims to look at the magnitude of job risks, knowledge, attitudes, sexual behavior, economic status, access to health services, and beliefs about the incidence of syphilis. The research method used is analytic observational using a case-control study design. The population in this study were all patients with syphilis in RSUP Dr. Wahidin Sudirohusodo and at the Rehabilitation Service Center for the Mattirodeceng Social Service, South Sulawesi Province. The research sample was 150 respondents, namely 50 syphilis case respondents and 100 control respondents. The sampling technique uses non-probability sampling with the Purposive Sampling method. Data were analyzed using SPSS with Odds Ratio (OR), chi-square, and multiple logistic regression tests. The results showed that the variables that were risk factors for syphilis were occupation (OR=76,000) with (CI=95%, LL=24,421, and UL=236,521), knowledge (OR=10,945) with (CI=95%, LL= 4,537 and UL=26,445), attitude (OR=2,452) with (CI=95%, LL=1,099, and UL=5,467), sexual behavior (OR=147,429) with (CI=95%, LL=40,989, and UL=530,267), economic status (OR=19,581) with (CI=95%, LL=6,522, and UL=58,789), access to health services (OR=5,310) with (CI=95%, LL=2,329, and UL=12,107), trust (OR=0.334) with (CI=95%, LL=0.128, and UL=0.869). The logistic regression test shows that the variable that works is the most at risk for syphilis, with a risk of occurrence of 110,418 times. Health workers can collaborate with social services to provide information on reproductive health on an ongoing basis, as well as education about safe sex behavior for sex workers.