Preclinical studies have shown that photodynamic therapy (PDT) enhances immune responses. To examine the role of the direct effects of PDT in liver cancer with regard to enhancement of the antitumor response, we injected PDT-generated H22 liver cancer cell lysate (as a tumor vaccine) intradermally into Kunming mice. In the control group, the cell lysate was substituted with normal saline solution. A liver tumor model was established by the injection of H22 cell suspension. We found that the PDT-generated vaccine significantly increased the percentages of CD4(+), CD8(+), and CD19(+) cells, inhibited tumor growth, and prolonged the survival time. Our findings suggest that PDT-generated vaccines can significantly enhance the antitumor immune response and may have the potential to be used as an adjuvant therapy clinically.