The existence of disorders in the mother-infant relationship may affect both maternal mental health and child development. Several factors have been associated with these disorders, including environmental factors (psychosocial variables) and genetic factors, specifically related to maternal oxytocin receptor gene (OXTR). The aim of this study was to investigate the possible interactions between genetic and environmental factors in the mother-infant relationship, assessed by the Postpartum Bonding Questionnaire (PBQ). A total of 1,057 Brazilian mothers completed assessments of mother-infant relationship, stress, depression, psychiatric symptoms and socioeconomic indicators using standardized instruments and were genotyped for OXTR rs53576 and rs2254298. To test our causal model, structural equation modeling (SEM) was used by means of a two-step approach. The goodness-of-fit of the measure model (step 1) and of the causal model (step 2) were evaluated with the quality indexes: χ2/df; CFI; GFI; PCFI, PGFI; RMSEA and MECVI. Three models were tested, one without genes as moderators, and two models having OXTR rs53576 and rs2254298 genes as moderators. The first model revealed an acceptable fit (χ²/df=4.780; CFI=0.756; PCFI=0.716; GFI=0.823; PGFI=0.749; RMSEA=0.060; MECVI=5.926). The analysis of the regression weights revealed statistically significant paths between PBQ (representing the mother-infant relationship) and stress (β=0.33, p<0.001) and between PBQ and psychiatric symptoms (β=0.30, p<0.001). For the model with gene OXTR rs53576 as moderator (AA/AG or GG) the fit was acceptable (χ²/df=2.985; CFI=0.747; PCFI=0.707; GFI=0.791; PGFI=0.721; RMSEA=0.043; MECVI=7.620), and it had factorial invariance. Only the path “stress-PBQ†had differences between the groups (Z=-1.655; p<0.10). For the model with gene OXTR rs2254298 (AA/AG or GG) as moderator, the fit was also acceptable (χ²/df=3.001; CFI=0.744; PCFI=0.744; GFI=0.788; PGFI=0.717; RMSEA=0.044; MECVI=7.782), although there wasn’t factorial invariance. We concluded that stress and psychiatric symptoms affect the mother-infant relationship, and that the OXTR rs53576 gene moderates the stress of the relationship with the infant.