To assess the objective and subjective image quality, and respiratory motion of hepatocellular carcinoma with portal vein tumor thrombosis (PVTT) using the contrast-enhanced four-dimensional dual-energy computed tomography (CE-4D-DECT). For twelve patients, the virtual monochromatic image (VMI) derived from the CE-4D-DECT with the highest contrast to noise ratio (CNR) was determined as the optimal VMI (O-VMI). To assess the objective and subjective image quality, the CNR and five-point score of the O-VMI were compared to those of the standard VMI at 77 keV (S-VMI). The respiratory motion of the PVTT and diaphragm was measured based on the exhale and inhale phase images. The VMI at 60 keV yielded the highest CNR (4.8 ± 1.4) which was significantly higher (p = 0.02) than that in the S-VMI (3.8 ± 1.2). The overall image quality (4.0 ± 0.6 vs 3.1 ± 0.5) and tumor conspicuity (3.8 ± 0.8 vs 2.8 ± 0.6) of the O-VMI determined by three radiation oncologists was significantly higher (p < 0.01) than that of the S-VMI. The diaphragm motion in the L-R (3.3 ± 2.5 vs 1.2 ± 1.1 mm), A-P (6.7 ± 4.0 vs 1.6 ± 1.3mm) and 3D (8.8 ± 3.5 vs 13.1 ± 4.9 mm) directions were significantly larger (p < 0.05) compared to the tumor motion. The improvement of objective and subjective image quality was achieved in the O-VMI. Because the respiratory motion of the diaphragm was larger than that of the PVTT, we need to be pay attention for localizing target in radiotherapy.