Tumor recurrence and metastasis have become thorny problems in clinical tumor therapy. Vaccine-mediated antitumor immune response has emerged as a significant postoperative inhibition for tumor recurrence and metastasis. However, limited tumor antigens are not conducive to trigger complete antigen-specific T cell-mediated immune responses. Herein, the design of a hydrogel vaccine system containing a granulocyte-macrophage colony stimulating factor (GM-CSF), based on surgically removed tumor cell lysates, was reported. The hydrogel was formed by crosslinking tumor cell lysates and alginate at low temperatures. The GM-CSF was released from the hydrogel to recruit dendritic cells (DCs), which provided a completely personalized tumor antigen pool. They were combined to foster the production of powerful antigen-specific T cells. The personalized hydrogel was implanted at the surgical site and it stimulated the antitumor immune response for the inhibition of residual tumor cells. Delightfully, the personalized hydrogel inhibited the tumor recurrence and metastasis well in a post-surgical mice tumor model, in combination with a programmed death-ligand 1 antibody (αPD-L1). The results demonstrated that the development of a personalized hydrogel and a combination of αPD-L1 provided a new strategy to prevent tumor recurrence and metastasis.