Abstract Background MicroRNAs (miRNAs) are a novel class of short RNAs that are capable epigenetically regulating gene expression in eukaryotes. MicroRNAs have been shown to be dysregulated in a variety of cancers. The data on miRNA expression in cutaneous squamous cell carcinoma (cSCC) are very limited, and microarray-based miRNA expression profiles of cSCC have not yet been determined. Objective To describe differentially expressed miRNAs in cSCC. Methods Seven patients with cSCC were enrolled in the present study. Tumor biopsies ( n = 7) were taken from the center of each tumor. Adjacent healthy skin ( n = 7) was biopsied as a control (intraindividual control). miRNA expression profiles of all specimens were detected by microarray miRNA expression profiling based on miRBAse 16 scanning for 1205 potential human miRNA target sequences. The microarray results were confirmed by TaqMan quantitative real-time polymerase chain reaction (qRT-PCR). Results Non-stringent filtering with a non-adjusted p ≤ 0.05 revealed thirteen up-regulated and eighteen down-regulated miRNAs. Non-stringent filtering with a non-adjusted p ≤ 0.01 revealed three up-regulated (hsa-miR-135b, hsa-miR-424 and hsa-miR-766) and six down-regulated (hsa-miR-30a*, hsa-miR-378, hsa-miR-145, hsa-miR-140-3p, hsa-miR-30a and hsa-miR-26a) miRNAs in cSCC. Conclusion This study reveals differentially expressed miRNAs that may play a role in the molecular pathogenesis of cSCC and that are excellent candidates for further validation and functional analysis.