Objective To analyze the value of serum levels of miR-141-3p, miR-130a, miR-29a-3p, and miR-210 in predicting early neurological deterioration (END) in non-traumatic intracerebral hemorrhage. Methods The patients with non-traumatic cerebral hemorrhage who met the selection criteria and were admitted to Chengde Central Hospital between February 2021 and October 2022 were prospectively selected by convenience sampling method. The serum miR-141-3p, miR-130a, miR-29a-3p, and miR-210 levels upon admission and the occurrence of neurological deterioration within 24 h were collected, and the patients were divided into a deterioration group and a non-deterioration group according to whether neurological deterioration occurred. The correlation of serum miR-141-3p, miR-130a, miR-29a-3p, and miR-210 levels with the END of non-traumatic intracerebral hemorrhage and their predictive value to the END of non-traumatic intracerebral hemorrhage were analyzed. Results A total of 235 patient were enrolled. Of the 235 patients, 45 (19.1%) showed neurological deterioration and 190 (80.9%) showed no neurological deterioration. The levels of miR-141-3p and miR-29a-3p in the deteriorating group were significantly lower than those in the non-deteriorating group [(1.11±0.32) vs. (1.76±0.51) ng/mL, P<0.001; (1.19±0.31) vs. (1.71±0.51) ng/mL, P<0.001], and the levels of miR-130a and miR-210 were significantly higher than those in the non-deteriorating group [(5.13±1.11) vs. (3.82±1.03) ng/mL, P<0.001; (3.96±0.76) vs. (2.78±0.50) ng/mL, P<0.001]. Multivariate logistic regression analysis showed that serum miR-141-3p and miR-29a-3p levels were protective factors for the occurrence of END in non-traumatic intracerebral hemorrhage patients [odds ratio (OR)=0.513, 95% confidence interval (CI) (0.330, 0.798), P=0.003; OR=0.582, 95%CI (0.380, 0.893), P=0.013], and serum miR-130a and miR-210 levels were independent risk factors for that [OR=2.046, 95%CI (1.222, 3.426), P=0.007; OR=2.377, 95%CI (1.219, 4.638), P=0.011]. The area under the receiver operating characteristic curve was 0.857 [95%CI (0.760, 0.954)] in predicting the END of non-traumatic intracerebral hemorrhage by the combined probability of the serum miR-141-3p, miR-130a, miR-29a-3p, and miR-210 levels obtained by logistic regression, and the sensitivity was 86.7%, the specificity was 94.7%, the positive predictive value was 79.6%, and the negative predictive value was 96.8% according to the cut-off value of the prediction probability of the combined test. Conclusion The combined detection of serum miR-141-3p, miR-130a, miR-29a-3p, and miR-210 has a high predictive value in the occurrence of END in non-traumatic intracerebral hemorrhage patients.