This research aimed to evaluate the interaction between polymorphisms of ERα & ERβ and associated with psychosocial stress on menopausal women. It was a cross-sectional study, subject were 102 women aged 40-70 years who meet the inclusion criteria at the Obstetrics and Gynecology Education Hospital of Hasanuddin who agreed on filling questioner which have been determined. Then proceed with blood taking for the ERα and ERβ receptor polymorphisms. Genomic DNA was isolated from 1mL of EDTA anticoagulation edge blood sample using a salting-out procedure and examined interaction of polymorphisms receptors ERα and ERβ. The data were statistically analyzed using the chi-square test with p-value<0.05. This research showed that subjects who experienced psychosocial stress have the most ERα Pvull heterozygous Pp polymorphism, ERα Xbal homozygous recessive xx, and homozygous dominant ERβ AA. There is ERβ polymorphism relationship with the occurrence of psychosocial stress in menopausal women. But there is no relationship between polymorphisms ERα Pvull, ERα Xbal, as well as the interaction between polymorphisms of ERα and ERβ with the occurrence of psychosocial stress in menopausal women. ERβ polymorphism relationship the occurrence of psychosocial stress in menopausal women.