Objective To explore the correlation between lncRNA TUG1 and Mir-219 and the development of ischemic stroke. Methods Sixty patients with acute ischemic stroke admitted from December 2020 to December 2021 were divided into ischemic stroke (IS) group and progressive ischemic stroke (PIS) group according to their clinical manifestations, and healthy people in the same period were included as the control group. Blood samples of patients in the observation group were collected on the day of admission and the 7th day to detect the levels of inflammatory indicators, immune indicators, lncRNA TUG1 and Mir-219, and the differences of the above indicators in different groups were compared. The correlation of inflammatory indicators and immune indicators with Mir-219 and lncRNA TUG1 was compared. The influencing factors of PIS were analyzed. The changes of the above indexes in PIS group were compared. The influencing factors of PIS group were analyzed 7 days after admission. Results There was no significant difference in gender, age and BMI among IS group, PIS group and control group (P>0.05), while there were significant differences in history of diabetes and hypertension (P<0.05). The lncRNA TUG1, inflammatory indicators, CD8+ and nCD64 in the IS and PIS groups were significantly higher than those in the control group (P<0.05). The levels of lncRNA TUG1, inflammatory indicators, CD8+ and nCD64 in PIS group were significantly higher than those in IS group (P<0.05). The Mir-219, CD4+ and CD4+/CD8+ levels in the IS and PIS groups were significantly lower than those in the control group (P<0.05). The Mir-219, CD4+ and CD4+/CD8+ levels in PIS group were significantly lower than those in IS group (P<0.05). The expression of lncRNA TUG1 was positively correlated with CRP, PCT, IL-6, IL-8, CD8+ and nCD64 (P<0.05), and negatively correlated with CD4+ (P<0.05). The expression of Mir-219 was negatively correlated with CRP, PCT, IL-6, IL-8, CD8+ and nCD64, P<0.05, and positively correlated with CD4+, P<0.05. History of diabetes, hypertension, lncRNA TUG1, CD8+, nCD64, CRP, PCT, ESR, IL-6, IL-8 and TNF-α were independent risk factors for PIS, while CD4+, CD4+/CD8+ and Mir-219 were protective factors for PIS. The expression levels of CRP, PCT, IL-6, IL-8, CD8+, nCD64 and lncRNA TUG1 were significantly increased compared with the first day (P<0.05), while CD4+ and Mir-219 were significantly decreased compared with the first day (P<0.05). LncRNA TUG1, CD8+, nCD64, CRP, PCT, IL-6 and IL-8 were independent risk factors for the progression of patients in PIS group, while CD4+ and Mir-219 were protective factors for the progression of patients in PIS group. Conclusions lncRNA TUG1 and Mir-219 are significantly correlated with the progression of ischemic stroke. The up-regulation of lncRNA TUG1 is an independent risk factor of PIS, and the up-regulation of Mir-219 is a protective factor of PIS. The effect of lncRNA TUG1 on the disease may be achieved by affecting the level of oxidative stress.