How to enhance the therapeutic efficacy of human cytokine induced killers cell (CIK) has become a great challenge. Herein, we report for the first time that human CIK cells loaded with gold nanoprisms were successfully used for targeted photoacoustic imaging, enhanced immunotherapy and photothermal therapy of gastric cancer in vivo. Gold nanoprisms were synthesized and modified with PEG; human CIK cells were prepared and incubated with PEGylated gold nanoprisms (Au GNPrs), and then the effects of human CIK cells labeled with Au NPrs on gastric cancer MGC 803 cells were evaluated and further used for targeted photoacoustic imaging, immunotherapy and photothermal therapy of gastric cancer in vivo in mice models. Results showed that PEGylated Au NPrs could be uptaken high-efficiently by human CIK cells, resultant human CIK cells labeled with AuNPrs could inhibit the growth of gastric cancer MGC 803 cells actively by induced apoptosis and G1 phase arrest, and actively target and accumulate the tumor sites in gastric cancer-bearing nude mice. Enhanced synergistic therapeutic efficacy was demonstrated with the maximal inhibition of tumor through a combination of CIK cells-based immunotherapy for three days and then a continuous gold nanoprisms-based photothermal therapy. In conclusion, human CIK cells labeled with PEGylated Au NPrs can target gastric cancer cells in vivo, enhance immunotherapy and photothermal therapy efficacy, and have a great potential in applications such as targeted imaging, immunotherapy and photothermal therapy of gastric cancer in the near future.