Defense mechanisms resulting from the interaction between biological factors and the environment have been established. In genetic studies, dopamine genes have been recognized to play an important role in the determination of defense mechanisms. DARPP-32 (dopamine- and cAMP-regulated phosphoprotein) plays a central role in the biology of dopamine-receptive neurons; its coding gene (PPP1R1B) has been linked to psychological and psychopathological traits. Here, we aimed to explore the association between PPP1R1B polymorphisms and defense mechanisms measured using the 88-item Defense Style Questionnaire in 400 healthy Chinese-Han subjects. Of the three polymorphisms examined, rs12601930 was associated with projection (P = 0.028) and splitting (P = 0.032), while rs3764352 was associated with splitting (P = 0.042). No significant association was found between rs879606 and defenses. When analyzed separately by gender, no significant association between defense mechanisms and PPP1R1B polymorphisms in males was observed. In females, however, rs12601930 was significantly associated with splitting (P = 0.018), and rs879606, with projection (P = 0.015), help-rejecting complaining (P = 0.030), and immature defense style (P = 0.031), while rs3764352 was not associated with any defense. The distribution of genotypes between the low- and high-scoring subgroups for each defense style showed no significant differences. Our results suggest that PPP1R1B polymorphisms are, at least partially, responsible for immature defenses.