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Background Long non-coding RNA (lncRNA) has the main role in gene regulation and it might serve as a potential biomarker in clinical practice. Malat1 and THRIL LncRNAs have been demonstrated to play key roles in inflammation and atherosclerosis. It was hypothesized that the Malat1 and THRIL expression increase in patients with atherosclerotic ischemic stroke (IS) with significant diagnostic value for discriminating IS from controls. Methods We evaluated Malat1 and THRIL expression on days 1,3, and 5 after stroke in 59 IS cases with small-vessel disease (SVD) and large artery atherosclerosis (LAA), and 63 controls. A real-time polymerase chain reaction was used for the evaluation of lncRNA expression. Results In patients with SVD or LAA, Malat1 and THRIL expression significantly were higher than the controls and mix model analysis showed significantly higher expression of lncRNAs on days 5 relative to days 1 and 3 after stroke while the positive correlation was also detected between Malat1 expression and time after stroke (r = 0.27, p = 0.03). After logistic regression analysis, elevated Malat1 and THRIL showed a significant positive association with the risk of SVD and LAA. We found Malat1 could be used as a diagnostic marker with an area under the curve of 0.78 (p < 0.001). Conclusion This was the first study that demonstrated the significant upregulation of THRIL from 24 hours after IS until 5 days. This upregulation may serve as a biomarker for the diagnosis of IS. To reach a reliable conclusion we need a larger sample size.