[Abstract] Objective: To investigate the relationship between serum programmed cell death factor 4 (PDCD4) levels and neurological deficits and prognosis in patients with acute ischemic stroke (AIS). Methods: A cohort of 110 AIS patients from the Department of Neurology, Affiliated Hospital 2 of Nantong University, admitted between June 2023 and March 2024, was retrospectively included as the study subjects. Based on the National Institutes of Health Stroke Scale (NIHSS) scores, patients were divided into a mild group (n=70) and a moderate to severe group (n=40). According to the modified Rankin Scale (mRS), patients were further divided into a good prognosis group (n=69) and a poor prognosis group (n=41). The demographic data (Age, Gender, history of diabetes, etc.) and clinical data (Neutrophil count, lymphocyte count, Neutrophil/lymphocyte ratio, etc.) of each group of patients were collected. Serum PDCD4 levels were measured using an Enzyme-linked immunosorbent assay (ELISA). The association between PDCD4 levels and NIHSS scores, mRS scores, and other inflammatory markers was analyzed in this study. Logistic regression analysis was used to infer the risk factors for moderate to severe neurological deficits and poor prognosis in AIS patients. Receiver operating characteristic (ROC) curves were used to evaluate the effectiveness of serum PDCD4 levels in predicting the degree of neurological deficit and prognosis of AIS patients. Results: In comparison to individuals with mild neurological deficits and good prognosis, those with moderate to severe neurological deficits and poor prognosis had considerably greater serum PDCD4 levels. PDCD4 levels showed a positive correlation with NIHSS scores, mRS scores, Hs-CRP, Procalcitonin, and Neutrophil/lymphocyte ratio. After controlling for confounding factors, PDCD4 remained an independent risk factor for acute ischemic stroke (AIS). Serum PDCD4 has a strong predictive value for neurological deficits and prognosis in individuals with AIS, according to ROC curve analysis. Conclusions: In AIS patients with moderate to severe neurological deficits and poor prognosis, serum PDCD4 levels are significantly elevated and can serve as an independent predictor of neurological deficits and prognosis.