Background: Micro-RNAs (miRNAs) play important roles in the development of different inflammatory conditions of the skin. However, few studies investigated the association between miR-146a and psoriasis. Aim of the work: This work aimed to study the association between miR-146a single-nucleotide polymorphism (SNP) rs2910164 and the risk of psoriasis and to study the association between levels of skin expression of miR-146a and the response to treatment. Methodology: The study was carried out on 120 patients with psoriasis and 60 control subjects. The miR-146a rs2910164 SNP was detected by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Levels of skin expression of miR-146a were detected by Real Time PCR before and 3 months after treatment with PUVA therapy. Results: Non significant association could be found between combined (CG+GG) genotypes and risk of psoriasis [OR (95% CI) = 0.81 (0.41-1.60)], (P=0.52). The level of miR-146a expression was significantly increased in patients compared to controls, with the highest level recorded in patients with CC genotype. There was a significant decrease in the miR-146a levels after treatment in both CC (P<0.001) & CG (P=0.01) genotypes but not in GG genotype (P=0.29). MiR-146a levels were higher in patients responding to treatment than non-responders (P<0.001). Also, there was significantly higher response to PUVA treatment in CC genotype (100%) than in CG genotype (50%) and GG genotype (20%) (P<0.001). In conclusion, no significant association could be found between combined rs2910164 genotypes (CG + GG) and risk of psoriasis. Moreover, measuring miR-146a level and knowing patients' genotype could be useful predictors of therapeutic response.