5-Aminolevulinic (5-ALA) acid photodynamic therapy (PDT) is a treatment for actinic keratosis and has been studied as a treatment for non-invasive cutaneous squamous cell carcinoma (cSCC). PDT induces apoptosis and necrosis in actinic keratosis and cSCC. 5-ALA blue light PDT may modulate gene expression and pathways in surviving cells. In this study, differential gene expression and pathway analysis of cSCC and human dermal fibroblasts were compared before and after 5-ALA blue light PDT using RNA-Sequencing. No genes were differentially expressed after correcting for multiple testing (FDR <0.05). As a result, transcription factor, gene enrichment, and pathway analysis were performed with genes identified before multiple testing (p<0.05). Pathways associated with proliferation and carcinogenesis were downregulated. These findings using 5-ALA blue light PDT are similar to previously published studies using methyl-aminolevulinic and red light protocols, indicating that surviving residual cells may undergo changes consistent with a less aggressive cancerous phenotype.