The single nucleotide polymorphism (SNP) rs4731702 in the KLF14 transcription factor gene has been associated with type 2 diabetes mellitus (T2DM) and HDL-c concentrations. The aim of the present study was to determine the distribution of KLF14 rs4731702 SNP and evaluate the association between this SNP and serum lipid profile in T2DM patients in a patient population at San Luis province, Argentina. A total of 73 volunteers (26 T2DM patients and 47 healthy age-matched controls) were genotyped for KLF14 rs4731702 SNP by Tetra Primer ARMS-PCR. The KLF14 genotypes distribution among study groups was not significantly different. In T2DM patients, there was a difference in HDL-c values and TC/HDL-c ratio, with T carriers of the rs4731702 SNP (non C/C) having higher HLD-c and lower TC/HDL-c ratio values than C/C homozygotes (p = 0.0047 and 0.0041, respectively). HDL-c levels were higher in diabetic patients, without dyslipidemia, carrying the genotype non- C/C (p = 0.023). Conversely, TC and LDL-c levels were lower in diabetic patients, without dyslipidemia, in non-C/C carriers (p < 0.001). The results of the current study showed that T2DM is characterized by dyslipidemia, and that the alterations observed in the lipoprotein might be related to lower KLF14 activity in diabetic patients as a consequence of C/C genotype and insulin resistance.