Objective To observe the expression of serum interleukin-12 (IL-12) and amyloid A (SAA) in patients with ST segment elevation myocardial infarction (STEMI), and to analyze its impact on the prognosis of STEMI patients after percutaneous coronary intervention (PCI). Methods Sixty-two patients with STEMI treated in Shangqiu Hospital of Traditional Chinese Medicine of Henan Province from May 2019 to May 2021 were selected as the research subjects, all patients were treated with PCI in our hospital and gained results of 1 month of follow-up after operation. At 1 month of follow-up, coronary angiography was performed to evaluate the coronary stenosis of patients, as a short-term prognostic indicator. The patients were divided into a poor prognosis group and a good prognosis group and serum levels of IL-12 and SAA were detected of patients at admission, asked and recorded the baseline data of patients. The influence of serum IL-12 and SAA levels on the prognosis of STEMI patients after PCI was analyzed. Results The serum levels of IL-12 and SAA in the poor prognosis group were higher than those in the good prognosis group, with a statistical significant difference (P<0.05); through Logistic regression analysis, the results showed that the overexpression of preoperative serum IL-12 and SAA had a certain impact on the poor prognosis of STEMI patients after PCI (P<0.05). Conclusion The overexpression of serum IL-12 and SAA has certain influence on the poor prognosis of STEMI patients after PCI.