Lactoferrin and CXCR1 genes are involved in immune responses related to mastitis infection. In this study, the polymorphism and association of lactoferrin (LF) and CXCR1 genes with milk somatic cell counts, as an indicator for mastitis detection, were investigated in Guilan native cow (Taleshi breed) using DNA blood samples of 100 cows from three different geographical zones (west, center, and east of Guilan province). The LF gene with a 301 bp fragment and CXCR1 with a fragment of 311 bp were amplified through PCR by using their specific primers. Then LF polymerase chain reaction (PCR) product was digested by EcoRI enzyme due to a single nucleotide polymorphism (SNP) at the related position (T>C) in intron 6 of LF and CXCR1 PCR product by BaeGI enzyme due to G > C SNP at position +735. Two alleles and three geno-types were observed for both genes in the studied populations. The observed genotypic frequencies of AA, AB, and BB were 52, 39, and 9% for LF and 67, 12, and 20% for CXCR1 locus, respectively. Three geno-types of LF locus were under Hardy-Weinberg equilibrium (P˃ 0. 05) but it was not for CXCR1 locus. The mean of somatic cell counts was 138 × 103/mL, much lower than the reported data of pure-bred and cross-bred cattle. Although there was no significant association (P<0. 05%) between LF genotypes and somatic cell score (SCS), there was a tendency for association (P<0. 1). The CXCR1c. +735 genotype had a signifi-cant association (P<0. 05) with SCS. Sampling from different regions did not show a significant effect on SCS. The fix effects including lactation month, age, and lactation number had also no significant effect on SCS of the studied native cow.