Aim To investigate the correlation between serum long-chain non-coding RNA GAS5 (lncRNA GAS5) level and in-stent restenosis in patients with acute ST-segment elevation myocardial infarction (STEMI). Methods 144 patients with STEMI who received selective percutaneous coronary intervention were selected, and according to the follow-up results, the patients were divided into 27 cases of in-stent restenosis (ISR) group and 109 cases of non-ISR group, with 8 cases lost. The clinical data of patients with STEMI were collected. The level of serum lncRNA GAS5 in all patients after percutaneous coronary intervention was measured by real-time quantitative PCR (qRT-PCR). Results Compared with non-ISR group, the proportions of smokers before operation and complicated diabetic, total bilirubin (TBIL), levels of total cholesterol (TC) and low density lipoprotein cholesterol (LDLC) in serum in ISR group were increased (P＜0.05), and the level of lncRNA GAS5 in serum was decreased (P＜0.05); The incidence of ISI in low level of GAS5 was higher than that in the patients with high level of lncRNA GAS5 (P＜0.05), and the average time of no restenosis was shorter (P＜0.05); Logistic regression analysis showed that low level of lncRNA GAS5 was a risk factor of in-stent restenosis in patients with STEMI. Conclusion The level of lncRNA GAS5 is down-regulated in the serum of in-stent restenosis patients with STEMI, and it is a risk factor of in-stent restenosis patients with STEMI.