<p>Chemokines-like factor 1 (CKLF1) possesses chemokine-related biological functions, and overproduction of CKLF1 may exacerbate inflammatory response, thereby worsening neurological impairments after acute brain injury diseases. The aim of this study was to determine its ability to predict early neurological deterioration (END) and 90-day poor prognosis after spontaneous intracerebral hemorrhage (sICH). A total of 129 sICH patients participated in this prospective cohort study. Serum CKLF1 levels were measured at admission in all patients and 129 healthy controls. Meanwhile, serum of CKLF1 levels of 50 patients were also measured at days 1, 2, 3, 5 and 7 after admission. Glasgow coma scale (GCS) scores and hematoma volumes were used to assess hemorrhage severity. END and postinjury 90-day poor prognosis [modified Rankin scale (mRS) scores 3–6] were observed as outcome variables. Multifactorial analyses were performed to determine the correlation of serum CKLF1 levels with disease severity and the association of neurofunctional prognosis. Serum CKLF1 levels in patients with sICH were elevated at admission, peaked on day 2, then gradually decreased and were significantly higher than those in healthy controls up to 7 days after sICH. Serum CKLF1 levels were independently correlated with hematoma volume, GCS scores and mRS scores. Meanwhile, serum CKLF1 levels were linearly correlated with the likelihood of not only developing END but also 90-days poor prognosis after sICH, and showed a strong discriminatory efficiency under the receiver operating characteristic curve. Serum CKLF1 levels, coupled with GCS scores and hematoma volumes were the independent predictors of END and 90-day poor prognosis. The three independent predictors were consolidated to establish two models for END and poor prognosis separately, which were visually delineated by nomograms. A series of statistical methods, such as calibration curve, decision curve, and ROC curve, were applied for validating the models’ stability, clinical fit, and discriminatory efficiency. Serum CKLF1 levels are prone to increase significantly shortly after sICH. Serum CKLF1 levels are independently associated with disease severity, occurrence of END, and development of 90-day poor prognosis after stroke, suggesting that serum CKLF1 may be a potential biomarker of sICH.</p><p><?noindent??><b>Clinical trial number</b> Not applicable.</p>