PURPOSE: To evaluate whether intraprocedural 3D quantification of Lipiodol deposition on cone-beam computed tomography (CBCT) can predict tumor response on follow-up contrast-enhanced magnetic resonance imaging (CE-MRI) in patients with hepatocellular carcinoma (HCC) treated with conventional transarterial chemoembolization (cTACE). MATERIALS AND METHODS: This IRB approved, retrospective analysis included 36 patients with 51 HCC target lesions, who underwent cTACE with CBCT. CE-MRI was acquired at baseline and 1 month after cTACE. Overall tumor volumes as well as intratumoral Lipiodol volumes on CBCT were measured and compared with the overall and necrotic (non-enhancing) tumor volumes on CE-MRI using the paired student's t test. Tumor response on CE-MRI was assessed using modified response evaluation criteria in solid tumors (mRECIST). A linear regression model was used to correlate tumor volumes, Lipiodol volumes, and the percentage of Lipiodol deposition on CBCT with the corresponding parameters on CE-MRI. Nonparametric spearman rank-order correlation and trend test were used to correlate the percentage of Lipiodol deposition in the tumor with tumor response. RESULT: A strong correlation between overall tumor volumes on CBCT and CE-MRI was observed (R(2) = 0.986). In addition, a strong correlation was obtained between the volume of Lipiodol deposition on CBCT and tumor necrosis (in cm(3)) on CE-MRI (R(2) = 0.960), and between the percentage of Lipiodol deposition and tumor necrosis (R(2) = 0.979). Importantly, the extent of Lipiodol deposition (in percentage of total tumor volume) correlated strongly with tumor response on CE-MRI (Spearman rho = 0.84, p < 0.001). CONCLUSIONS: Intraprocedural 3D quantification of Lipiodol deposition on CBCT can be used to predict tumor response on follow-up CE-MRI.