This study reports a comparative assessment of the biological impact of a heated tobacco aerosol from the Carbon-Heated Tobacco Product (CHTP) 1.2, and smoke from a combustible 3R4F cigarette on human organotypic small airway epithelial tissue exposed at the air-liquid interface. The miRNome was characterized using Affymetrix GeneChip™ miRNA 4.0 Array. This dataset contains the statistics resulting from the comparison of treatment and control groups. The miRNA array datasets are available in the Area Express repository under the accession number E-MTAB-6611.