Objective? To explore the effects of Benzathine penicillin in the treatment of syphilis during pregnancy in different periods on the clinical efficacy, immune function and pregnancy outcome, to provide basis for clinical treatment. Methods The clinical data of 80 syphilis during pregnancy in Suzhou national hi-tech district collected by Suzhou National Hi-tech District (Huqiu District) Center for Disease Control and Prevention from December 2019 to December 2021, through the management information system for prevention of mother-to-child transmission of HIV, syphilis and hepatitis B were retrospectively analyzed, they were divided into the middle and late pregnancy group (gestational week > 12 weeks) and the early pregnancy group (gestational week ≤?12 weeks) according to the different of gestational weeks, with 40 in each group. Patients in the both groups received the treatment of Benzathine penicillin. The clinical efficacy, immune function indexes before and after treatment, neonatal Apgar score 1 and 5 minutes after delivery, as well as pregnancy outcomes, the result of maternal and infant rapid plasma reagin circle card test (RPR), the diagnosis of congenital syphilis in newborns were compared between the two groups. Results? The total clinical effective rate in the early pregnancy group was significantly higher than that in the middle and late pregnancy group; compared with before treatment, the percentage of CD4+ , CD4+ /CD8+ ratio of patients in the two groups significantly increased after treatment, and the early pregnancy group was significantly higher than the middle and late pregnancy group, the percentage of CD8+ of patients significantly decreased, and the early pregnancy group was significantly lower than the middle and late pregnancy group; the full-term delivery rate in the early pregnancy group was significantly higher than that in the middle and late pregnancy group; the proportion of newborns with Apgar score ≥?7 1 and 5 minutes after delivery in the early pregnancy group was significantly higher than that in the middle and late pregnancy group; the proportion of maternal and infant RPR titer≥1∶8 in the early pregnancy group was significantly lower than that in the middle and late pregnancy group;the incidence of neonatal congenital syphilis in the early pregnancy group was significantly lower than that in the middle and late pregnancy group (all P<0.05). Conclusion? Compared with the treatment in the middle and late pregnancy, the treatment of Benzathine penicillin in the early pregnancy for patients with syphilis during pregnancy can improve the clinical efficacy of patients more effectively, enhance the patients’ immune function, and help to improve the pregnancy outcome and newborn health, with a remarkable effect.