Objective To investigate the serum levels of angiopoietin-like protein-3 （ANGPTL3） and nuclear factor of active T cells cytoplasmic 1 （NFATc1） in patients with cerebral infarction， and their relationship with the severity and prognosis of the disease. Methods A total of 180 patients with cerebral infarction set as cerebral infarction group who underwent treatment in our hospital from January 2021 to January 2023 were collected as research subjects. According to the NIHSS score， the patients were divided into mild group （n = 68）， moderate group （n = 76）， and severe group （n = 36）， respectively. According to the mRS Score， they were divided into a good prognosis group （n = 117） and a poor prognosis group （n = 63）. Another 180 healthy people were enrolled as the control group. The levels of serum ANGPTL3 and NFATc1 were compared among the groups. Multivariate logistic regression was adopted to analyze the influencing factors of prognosis in the patients with cerebral infarction. Receiver operating characteristic （ROC） curve was used to analyze the predictive value of serum ANGPTL3 and NFATc1 on the prognosis of the patients with cerebral infarction. Results The serum levels of ANGPTL3 and NFATc1 in the cerebral infarction group were significantly higher than those in the control group （P < 0.05）. The levels of serum ANGPTL3 and NFATc1 were significantly increased in an ascending order across the mild， moderate， and severe groups （P < 0.05）. The volume of cerebral infarction， white blood cell count， ANGPTL3， and NFATc1 levels in the patients with poor prognosis were significantly higher than those in the patients with good prognosis （P < 0.05）. Regression analysis showed that cerebral infarction volume， white blood cell count， ANGPTL3， and NFATc1 were the influencing factors of the prognosis of cerebral infarction patients （P < 0.05）. The levels of ANGPTL3 and NFATc1 together were more effective than they were alone in predicting the prognosis of the patients with cerebral infarction （Z _{combined detection - ANGPTL3} = 3.345， Z_{combined detection - NFATc1} = 2.898； P = 0.001， 0.004）. Conclusion The serum levels of ANGPTL3 and NFATc1 in patients with cerebral infarction are significantly increased， with the increase amplitude depending on the severity of the condition. ANGPTL3 and NFATc1， when combined， are more effective and valuable for predicting the prognosis of cerebral infarction patients.