Objective To explore the relationship between peripheral blood systemic immune-inflammation index (SII), ratio of C-reactive protein/albumin (CRP/ALB) and the severity as well as prognosis of patients with diabe-tic foot ulcer (DFU). Methods Clinical data of 157 DFU patients admitted to a hospital from June 2020 to December 2021 were retrospectively analyzed. According to the 6-month follow-up results, they were divided into the good prognosis group (n=108) and the poor prognosis group (n=49). The relationship between SII, CRP/ALB and di-sease severity as well as the predictive effect on the prognosis of DFU patients was analyed, and risk factors for poor prognosis in DFU patients were identified. Results SII and CRP/ALB in DFU patients gradually increased with the increase of Wagner's grade, aggravation of infection and ischemia (all P < 0.05). SII was positively correlated with white blood cell count, CRP, glomerular filtration rate and glycated hemoglobin, while negatively correlated with albumin and ankle-brachial index (all P < 0.05). The best cut-off point of SII and CRP/ALB for predicting the poor prognosis of DFU patients were 427.5 and 3.05, respectively, and the area under the receiver operating characteristic curve were 0.797 (95%CI: 0.715-0.879) and 0.869 (95%CI: 0.809-0.930, both P < 0.05), respectively. Logistic regression analysis showed that C-reactive protein, albumin, glomerular filtration rate, ankle-brachial index, glycated hemoglobin, SII and CRP/ALB were independent factors for the poor prognosis of DFU patients (all P < 0.05). Conclusion SII and CRP/ALB are related with the severity of the disease in DFU patients. They are factors for poor prognosis, and can be used to evaluate the prognosis of DFU patients.