Objective To investigate the effect of Homeobox (HOX) protein 13 on cell proliferation and apoptosis in patients with diabetic foot. Methods 79 patients were selected as the research object, which were divided into diabetes foot group (n=60), diabetes non diseased foot group (n=19), and healthy control group (n=60). The clinical characteristics and correlation of HOX13 among the three groups were compared and analyzed. The expression of HOX13 among the three groups was determined by immunohistochemistry. Western blot was used for HOX13 protein expression. Cell proliferation was detected by CCK-8 and EDU assay. Cell apoptosis was detected by flow cytometry. In vitro cell models were constructed and divided into HOX13 knockout group (transfected with HOX13 plasmid), HOX13 overexpression group (transfected with HOX13 plasmid), and blank group (without any treatment). Results Age, disease course, white blood cell count, FG, HbA1c, TNF-β, hs-CRP, 1L-6, 1L-4 in non-diseased foot group were significantly lower than those in diabetic foot group (P<0.05). Age, disease course, white blood cell count, FG, HbA1c, TNF-β, hs-CRP, 1L-6, 1L-4 in healthy control group were significantly lower than those in non-diseased foot group (P<0.05). The ankle-brachial index, hemoglobin and albumin in non-diseased foot group were significantly higher than those in diabetic foot group (P<0.05). The positive expression of HOX13 was negatively correlated with age, disease course, white blood cell count, FG, HbA1c, TNF-β, hs-CRP, 1L-6, 1L-4 (P<0.05). Ankle-brachial index and albumin were positively correlated with HOX13 (P<0.05). Immunohistochemical results showed that HOX13 expression was significantly decreased in diabetic foot group compared with non-diseased foot group and healthy control group. Compared with blank group, TNF-β, hs-CRP, 1L-6 and 1L-4 were significantly higher in HOX13 knockout group (P<0.05), while significantly lower in overexpression group (P<0.05). Compared with blank group, the protein expressions of Caspase-3, Caspase-9 and Bax were significantly higher in HOX13 knockout group, and significantly lower in overexpression group (P<0.05), the protein expression of Bcl-2 in HOX13 knockout group was significantly lower (P<0.05), and significantly higher in overexpression group (P<0.05). Flow cytometry showed that HOX13 knockout significantly increased cell apoptosis (P<0.05). The results of CCK-8 experiment showed that the proliferation state of HOX13 overexpression group was significantly increased compared with that of over knockout group and blank group (P<0.05). Compared with blank group, the number of EDU labeled cells in knockout group was significantly decreased (P<0.05), while that in overexpression group was significantly increased (P<0.05). Conclusion The expression of HOX13 is significantly decreased in the tissues of diabetic foot patients. High expression of HOX13 can promote the proliferation of diabetic foot fibroblasts, inhibit their apoptosis, and inhibit the expression of inflammatory factors. HOX13 may be related to the occurrence and progression of diabetic foot disease