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Background: Intracranial progression is considered an important cause of treatment failure in anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) patients. Recent advances in targeted therapy and radiomics have generated considerable interest for the exploration of prognostic imaging biomarkers to predict the clinical course. Here, we developed a magnetic resonance imaging (MRI) radiomic signature that can stratify survival and intracranial progression.Methods: We analyzed 87 brain metastatic lesions in 24 ALK-positive NSCLC patients undergoing ALKinhibitor ensartinib therapy and divided them into training (n=61) and validation (n=26) sets. Radiomic features were extracted and screened from contrast-enhanced MR images. Combined with these selected features, the Rad-score was calculated with multivariate logistic regression. The predictive model and Rad-score performance were assessed in the training set and validated in the validation set; decision curve analysis was performed with the combined training and validation sets to estimate Rad-score's patient-stratification ability.Results: The prediction model constructed with nine selected radiomic features could predict intracranial progression within 51 weeks (AUC =0.84 and 0.85 in the training and validation sets, respectively), while clinical and regular MRI characteristics were independent of progression (P>0.05). The decision-curve analysis showed that the radiomic prediction model was clinically useful. The Kaplan-Meier analysis showed that the progression-free survival (PFS) difference between the high-and low-risk groups distinguished by the Rad-score was significant (P=0.017).Conclusions: Radiomics may provide prognostic information and improve pretreatment risk stratification in ALK-positive NSCLC patients with brain metastases undergoing ensartinib treatment, allowing followup and treatment to be tailored to the patient's individual risk profile.