To provide the poultry industry with effective mitigation strategies, the effects of cetylpyridinium chloride (CPC) on the reduction of Salmonella Infantis, hilA expression, and chicken skin microbiota were evaluated. Chicken breast skins (4×4 cm; N = 100, n = 10, k = 5) were inoculated with Salmonella (Typhimurium or Infantis) at 4°C (30min) to obtain 108 CFU/g attachment. Skins were shaken (30s), with remaining bacteria being considered firmly attached. Treatments were applied as 30s dips in 50 mL: no inocula-no-treatment control (NINTC), no treatment control (NTC), tap water (TW), TW+600 ppm PAA (PAA), or TW+0.5% CPC (CPC). Excess fluid was shaken off (30s). Samples were homogenized in nBPW (1 min). Samples were discarded. Salmonella was enumerated and Log10 transformed. Reverse transcriptase-qPCR (rt-qPCR) was performed targeting hilA gene and normalized using the 2-ΔΔCt method. Data were analyzed using one-way ANOVA in RStudio with means separated by Tukey’s HSD (P≤0.05). Genomic DNA of rinsates was extracted, 16S rRNA gene (V4) was sequenced (MiSeq), and data analyzed in QIIME2 (P≤0.05 and Q≤0.05). CPC and PAA affected Salmonella levels differently with CPC being effective against S. Infantis compared to TW (P<0.05). Treatment with CPC on S. Infantis-infected skin altered the hilA expression compared to TW (P<0.05). When inoculated with S. Typhimurium, there was no difference between the microbiota diversity of skins treated with PAA and CPC; however, when inoculated with S. Infantis, there was a difference in the Shannon’s Entropy and Jaccard Dissimilarity between the two treatments (P<0.05). Using ANCOM at the genus level, Brochothrix was significant (W = 118) among skin inoculated with S. Typhimurium. Among S. Infantis inoculated, Yersiniaceae, Enterobacterales, Lachnospiraceae CHKCI001, Clostridia vadinBB60 group, Leuconostoc, Campylobacter, and bacteria were significant (40<W>8). CPC and PAA-treated skins had lowest relative abundance of the genera. In conclusion, CPC mitigated Salmonella Infantis, altered hilA expression, and influenced the chicken skin microbiota.