Hepatocellular carcinoma (HCC) is a common malignancy with a poor prognosis. This investigation examined whether dendritic cell–based immunotherapy can treat murine HCC effectively. Bone marrow–derived dendritic cells were propagated from C57BL/10J mice in GM-CSF (4 ng/mL) and interleukin (IL)-4 (1,000 μ/mL). The dendritic cells were pulsed with a Hepa1-6 lysate overnight and employed to treat murine HCC. For in vivo study, HCC was created by inoculation of hepa1-6, 5 × 105 cells, in the flank of C57BL/10J mice. HCC were categorized into small (3 × 3-mm) and large (5 × 5-mm) tumors. These HCC were treated by dendritic cells intravenously, twice at weekly intervals. The results revealed that lymphocytes could be gathered around small HCC after administration of Hepa1-6 lysate–pulsed dendritic cells. Seven of 12 (58.3%) small HCC could be eradicated completely by dendritic cell–based immunotherapy, and 33.3% of the small tumors responded to immunotherapy partially which were held in a stable condition for 34.0 ± 7.4 days before the tumors regrew. For large HCC, lymphocytes did not gather around the tumors, and the tumors cannot be eradicated effectively by dendritic cells. However, dendritic cell–based immunotherapy could slow down the growth rate of large tumors (116.2 ± 91.4 mm3 vs. 234.0 ± 149.1 mm3 of the control on day 7, P = .043; and 280.3 ± 224.7 mm3 vs. 870.0 ± 418.9 mm3 of the control on day 17, P < .001). Conclusively, dendritic cells pulsed with a Hepa1-6 lysate can be employed to treat small HCC in vivo effectively. However, the efficacy of dendritic cell–based immunotherapy decreases while tumors grow.