Poly(amidoamine) (PAMAM) dendrimers are good candidates for nucleic acid delivery with theirwell-defined characteristics. MicroRNA mediated regulation of biological process is also active an area ofinvestigation. Fibroblast cells, such as MRC-5, are one of the cell lines used in biological researches due totheir hard to transfect nature. In this two-staged study, cystamine core generation 5 PAMAM dendrimerswere synthesized and fluorinated with pentafluoropropionic anhydride and subsequently tested as miRNAdelivery reagent on MRC-5 cells. Effect of fluorination against to naked generation 5 dendrimer ontransfection efficiency was also investigated by molecular docking and quantitative structure-activityrelationship calculations. Structural characterization of the synthesized dendrimers was verified byspectroscopic techniques. Gel retardation assay, particle size and transmission electron microscopy resultsdemonstrated polyplex formation of fluorinated dendrimers with miRNA at nanoscale level. Zeta potentialvalues indicated non-aggregation and increased stability of the polyplexes. Prepared polyplexes withfluorinated dendrimer showed over 90% cell viability and transfection efficiency. In silico calculationsconfirmed the stable complexation with miRNA and good penetration capability into the cell.