Aim To investigate the correlation between triglyceride/high density lipoprotein cholesterol ratio (TG/HDLC) and carotid plaque instability in patients with ischemic stroke (IS). Methods 594 patients with acute IS treated in the Department of Neurology of Baoding First Central Hospital from January 2019 to January 2020 were included retrospectively. All subjects underwent ultrasound examination to understand the carotid plaque. According to the ultrasound results, the subjects were divided into non-plaque group (105 cases), stable plaque group (63 cases) and unstable plaque group (426 cases). The routine biochemical indexes and blood lipid indexes were detected by automatic biochemical analyzer, and the differences of risk factors, biochemical indexes and blood lipid were compared in each group. Logistic regression analysis was used to evaluate the influencing factors of carotid plaque instability, and the odds ratio (OR) and 95% confidence interval (95%CI) were calculated. Receiver operating characteristic (ROC) curve was used to analyze the predictive value of TG/HDLC for carotid plaque instability. Results Among the 594 patients with IS, 105 had no carotid stenosis and 489 had carotid stenosis, including 439 cases of mild stenosis, 20 cases of moderate stenosis, and 30 cases of severe stenosis. The male, body mass index (BMI), smoking history, drinking history, hemoglobin, TG/HDLC in unstable plaque group were higher than those in stable plaque group, and age, HDLC were lower than that in stable plaque group (P＜0.05). Multivariate Logistic regression analysis showed that TG/HDLC was an independent risk factor for carotid plaque instability (OR 1.8,5%CI 1.027～2.551, P＝0.038). ROC curve analysis showed that the area under the curve of TG/HDLC for predicting carotid plaque instability was 0.619 (95%CI 0.542～0.696), the best cut-off value was 1.60, the sensitivity was 35.4%, and the specificity was 84.1%. Conclusion TG/HDLC is an independent risk factor for carotid plaque instability in patients with IS, and it has a certain predictive value for carotid plaque instability.