In this work, the association between interleukin-6 (IL-6) and transforming growth factor (TGF-β1) single-nucleotide polymorphisms (SNPs) and the susceptibility to PCOS and their implication on plasma levels were studied. We genotyped IL-6 -174 G/C using mutagenically separated polymerase chain reaction (MS-PCR) and TGF-β1, +869 T/C and +915 G/C, using sequence-specific primer PCR (SSP-PCR) in 61 PCOS Egyptian patients and 80 controls. The plasma levels of IL-6 and TGF-β1 were measured using enzyme-linked immunosorbent assay (ELISA). Significant increase in the frequency of IL-6 (-174 G/C) CC (p < 0.001, odds ratio (OR) = 26.89) and GC (p < 0.01, OR = 4.32) genotypes, and C allele (p < 0.001, OR = 5.6) was found in PCOS patients compared to controls. Genotyping of TGF-β1 (+869 T/C) showed insignificant change in the distribution of all genotypes and alleles between controls and patients. Significant increase in the frequency of TGF-β1 (+915 G/C) GC genotype (p < 0.001, OR = 5.04) and C allele (p < 0.001, OR = 4.26) was noticed in PCOS patients compared to controls. PCOS patients had significantly higher level of IL-6 (p < 0.01) and significantly lower level of TGF-β1 (p < 0.001) compared to controls. IL-6 level significantly increased in PCOS patients with GC and CC (p < 0.001) genotypes while that of  TGF-β1 significantly increased only in PCOS patients having CC genotype (+869 T/C and +915 G/C). In conclusion, our preliminary findings showed a significant statistical association between the polymorphisms of TGF-β1 (+915 G/C) and IL-6 (-174 G/C) and PCOS risk. To the best of our knowledge, this is the first study regarding the association between IL-6 and TGF-β1 polymorphisms and PCOS susceptibility in Egyptians.