Yu-Ping-Feng-San (YPF) is a famous classical Chinese medicine formula known for its ability to boost immunity. YPF has been applied to enhance the immune status of tumor patients in clinical practice. However, there is still a lack of research on its immune regulatory effects and mechanisms in the tumor microenvironment. This study was designed to investigate the effects and mechanism of YPF on improving the immune suppression state of hepatocellular carcinoma (HCC) microenvironment. In an orthotopic mouse model of HCC, YPF improved the immune microenvironment of HCC immunosuppression, enhanced the maturation of dendritic cells (DCs), promoted the release of IL-12, and decreased the presence of JAK2, p-JAK2, STAT3, and p-STAT3 proteins in both tumor tissue and paracancerous tissues. YPF also could promote the maturation and reduce the activation of JAK2, p-JAK2, STAT3, and p-STAT3 proteins of mouse bone marrow-derived DCs induced by culture medium or tumor supernatant in vitro. Transient transfection of siRNA-STAT3 with DCs resulted in an increase in its maturation and its secretion of IL-12. On the whole, these combined effects of YPF served to ameliorate the HCC immune suppression microenvironment, which conducive to immune cells play the role of immune surveillance and killing liver cancer cells. The mechanisms of these combined effects were, at least in part, related to its inhibition of the activated JAK2-STAT3 signaling pathway in DCs within the HCC microenvironment.