Background: Homeobox A9 (HOXA9) has been implicated in acute myeloid leukemia and cancer breast but, little is known about HOXA9 expression in non- melanoma skin cancer (NMSC); basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC). Objective: The aim of the current work was to study HOXA9 expression in NMSC by immunohistochemical method.  Patients and Methods: This case-control study included a total of 45 cases with NMSC; 15 BCC and 30 SCC beside 45 age and sex-matched normal apparently healthy controls, selected from Dermatology, Andrology & Sexually transmitted diseases (STDs) Outpatient Clinic, Menoufia University Hospital, during the period December 2018 to June 2020. Clinical evaluation and histopathological evaluation confirmed the diagnosis of SCC and BCC. Results: Expression of HOXA9 in the overlying epidermis was positive in 83.3% of SCC cases with strong intensity in 68% and nucleocytoplasmic localization in 100%. HOXA9 was positive in 60% of BCC cases with mild intensity in 77.8% and nucleocytoplasmic localization in 100%. In control sections, HOXA9 was in all sections (100%) with strong intensity in 77.8%, and nucleocytoplasmic localization in all of them 100%. Regarding tumor islands; expression of HOXA9 was positive in 26 (86.7%) cases of SCC and was positive in 2 (13.3%) of BCC cases. There was significant higher HOXA9 H- score in control skin than NMSC (p < 0.001). Conclusions: It could be concluded that HOXA9 may be implicated in pathogenesis and may represent a target therapy for NMSC.