To investigate whether quantifications of apparent diffusion coefficient (ADC) on diffusion-weighted imaging (DWI) can predict overall survival (OS) in patients with liver-predominant metastatic colorectal cancer (CRC) following selective internal radiation therapy with 90Yttrium-microspheres (SIRT). Forty-four patients underwent DWI 19 ± 16days before and 36 ± 10days after SIRT. Tumour-size and intratumoral minimal ADC (minADC) values were measured for 132 liver metastases on baseline and follow-up DWI. Optimal functional imaging response to treatment was determined by receiver operating characteristics and defined as ≥22% increase in post-therapeutic minADC. Survival analysis was performed with the Kaplan-Meier method and Cox-regression comparing various variables with potential impact on OS. Median OS was 8months. The following parameters were significantly associated with median OS: optimal functional imaging response (18 vs. 5months; p < 0.001), hepatic tumour burden <50% (8 vs. 5months; p = 0.018), Eastern Cooperative Oncology Group performance scale <1 (10 vs. 4months; p = 0.012) and progressive disease according to Response and Evaluation Criteria in Solid Tumours (8 vs. 3months; p = 0.001). On multivariate analysis, optimal functional imaging response and hepatic tumour burden remained independent predictors of OS. Functional imaging response assessment using minADC changes on DWI may predict survival in CRC shortly after SIRT. • Relative minADC changes may predict survival in liver-predominant metastatic colorectal cancer following SIRT • Intratumoral minADC changes by ≥22 % were best to predict an improved overall survival • Functional imaging response assessment is feasible before anatomic tumour-size changes occur • minADC changes might guide future therapy management in sequential lobar radioembolization approaches.