Purpose <p>The objective of this study was to elucidate the relationship between two single nucleotide polymorphisms (SNPs) rs7176005 and rs6493497 in <i>CYP19</i> gene and the risk of polycystic ovary syndrome (PCOS) in Northern Chinese women.</p> Methods <p>In this case-control study, a total of 340 women with PCOS and 340 matched healthy controls were recruited. Polymerase chain reaction ligase detection reaction (PCR-LDR) method was used to investigate two SNPs (rs7176005 and rs6493497) in the 5’-flanking region of <i>CYP19</i> gene exon 1.</p> Results <p>We observed a significant association of rs7176005 and rs6493497 with reduced risk of PCOS. Compared with CC genotype, a significant association of CT genotype (<i>p</i> = 0.019), TT genotype (<i>p</i> &lt; 0.001) and combined CT + TT genotype (<i>p</i> &lt; 0.001) with reduced risk of PCOS was observed. The result of linkage disequilibrium analysis showed that these two SNPs are in complete linkage disequilibrium (<i>r</i>² = 1). For rs7176005 SNP, compared with CC genotype, CT, TT and CT + TT genotypes reduced the risk of PCOS. The age, BMI-adjusted <i>OR</i> were 0.650 (95% <i>CI</i> = 0.460–0.917), 0.158 (95% <i>CI</i> = 0.066–0.376) and 0.545(95% <i>CI</i> = 0.391–0.759), respectively.</p> Conclusions <p>These findings highlight a significant association between <i>CYP19</i> gene polymorphisms and PCOS susceptibility, implying potential protective effects of T and A alleles. Of course, the major limitation of this study is the sample size of the case-control study. Larger cohort studies are needed to confirm these findings and investigate the underlying causes.</p>