Aim To explore the expression and clinical significance of a novel long noncoding RNA n342721 (lncRNA n342721) in the serum of patients with acute myocardial infarction (AMI). Methods The expression of lncRNA in serum of 5 patients with AMI and 5 cases without coronary heart disease (non-CHD) was detected by using Human Transcriptome Array 2.0, and 6 up-regulated lncRNAs with different expression levels were screened out. Further verification and screening were carried out in serum of 20 patients with AMI and 20 cases with non-CHD and Jurkat T cells in vitro, and the most different lncRNA n342721 was selected for the study. In order to explore the clinical value of lncRNA n342721, the serum lncRNA n342721 expression and clinical data of 60 patients with AMI and 60 cases with non-CHD were analyzed. Furthermore, lncRNA n342721 was overexpressed and silenced at T cell level, then the changes of inflammatory cytokines such as interleukin-6 (IL-6), IL-10 and tumor necrosis factor α (TNF-α), and cholesterol transport related indexes such as liver X receptor β (LXR-β), ATP binding cassette transporter A1 (ABCA1) and ABCG1 were detected. Results Compared with non-CHD, 296 up-regulation and 74 down-regulation lncRNAs were detected among differentially expressed lncRNAs in the serum of AMI patients. Among the 6 selected lncRNAs, lncRNA n342721 was selected as the main research object, which had the greatest expression difference in serum and T cell levels. The results of quantitative real-time PCR showed that the expression of serum lncRNA n342721 in AMI group (n＝60) was significantly higher than that in non-CHD group (n＝60) (P＜0.05). Further logistic regression analysis showed that serum lncRNA n342721 was closely related to the occurrence of AMI. After construction of lncRNA n342721 overexpression lentivirus and transfection of T cells with small interfering RNA, it was found that, compared with the control group, the expressions of TNF-α and IL-6 increased in overexpression group (P＜0.05), the expressions of IL-10, LXR-β, ABCA1 and ABCG1 decreased (P＜0.05), the expressions of TNF-α and IL-6 decreased in silence group (P＜0.05), and the expressions of IL-10, LXR-β, ABCA1 and ABCG1 increased (P＜0.05). Conclusion As a new biomarker, serum lncRNA n342721 may promote the occurrence and development of AMI by promoting immune inflammatory response and inhibiting reverse cholesterol transport.