As a transcription factor belonging to the basic helix-loop-helix leucine-zipper subgroup, AP-4 can control target gene expression by altering cell signal transduction, and regulate growth, development, and cell apoptosis. Under pathological circumstances, it is involved in tumorigenesis. Herein, immunohistochemistry and real-time PCR were used to detect the transcription factor AP-4 expression in gastric cancer, and these data were examined for correlation with histology, pTNM stage, and prognosis. The AP-4 expression rate was 83.67% in a total of 98 gastric cancer tissues, which was significantly higher than 40.91% in non-neoplastic tissues; AP-4 mRNA relative expression shows a significant difference between gastric cancer and normal tissues, and AP-4 expression has a significantly positive correlation with the depth of tumor invasion (P < 0.0001), degree of tumor differentiation (P = 0.0058), lymph node metastasis (P = 0.0255), and pTNM stage (P = 0.001). Survival analysis showed that AP-4-positive patients' median survival time (12.60 months) was significantly shorter than that (41.40 months) of AP-4-negative patients. AP-4 expression in gastric cancer is associated with clinicopathological parameters of gastric cancer, such as differentiation, lymph node metastasis, depth of invasion (P = 0.0010), and pTNM stage. What's more, AP-4 overexpression indicated a worse prognosis for patients. So AP-4 may be a molecular marker to predict the progression and prognosis of the tumor.