There is little knowledge of the effect of inflammatory markers on the prognoses of hematoma expansion (HE) in patients with intracranial hemorrhage (ICH). We evaluated the impact of neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR) on HE and worse outcomes after acute ICH. This study included 520 consecutive patients with ICH from the registry database enrolled over 80 months. Patients’ whole blood samples were collected upon arrival in the emergency department. Brain computed tomography scans were performed during hospitalization and repeated at 24 h and 72 h. The primary outcome measure was HE, defined as relative growth >33% or absolute growth <6 mL. A total of 520 patients were enrolled in this study. Multivariate analysis showed that NLR and PLR were associated with HE (NLR: odds ratio [OR], [95% CI] = 1.19 [1.12–1.27], p < 0.001; PLR: OR, [95% CI] = 1.01 [1.00–1.02], p = 0.04). Receiver operating characteristic curve analysis revealed that NLR and PLR could predict HE (AUC of NLR: 0.84, 95% CI [0.80–0.88], p < 0.001; AUC of PLR: 0.75 95% CI [0.70–0.80], p < 0.001). The cut-off value of NLR for predicting HE was 5.63, and that of PLR was 23.4. Higher NLR and PLR values increase HE risk in patients with ICH. NLR and PLR were reliable for predicting HE after ICH.