This study aims to investigate the expression and correlations of the transcriptional repressors zincfingers and homeoboxes 2 (ZHX2), p53, and survivin in various malignant tumors. Immunohistochemistry was performed to detect the expression of ZHX2, p53, and survivin in the tumor tissues and corresponding paraneoplastic normal tissues of 36 cases of esophageal cancer, 38 cases of gastric cancer, 42 cases of lung cancer, and 38 cases of breast cancer. Their mutual correlations and relationships with clinicopathological features were also analyzed. The expression of ZHX2 in the above cancer tissues was higher than that in the corresponding paraneoplastic normal tissues, with statistically significant differences (P<0.05). In esophageal cancer, the expression of ZHX2 was related to the invasion depth of the tumor, while not being associated with the expressions of p53 and survivin. In gastric cancer the expression of ZHX2 was also related to the invasion depth of the tumor, but was positively correlated with the expression of p53 (P=0.02, r=0.376) and survivin (P=0.015, r=0.391). For lung cancer, the expression of ZHX2 was correlated with the presence or absence of mediastinal lymph node metastasis (P <0.05), and positively correlated with the expression of p53 (P=0.000, r=0.513). Finally, in the breast cancer samples, the expression of ZHX2 was related to the presence or absence of axillary lymph node metastasis (P<0.05), whilst not being linked to the expression of estrogen and prostaglandin. Therefore, the expression of ZHX2 correlated with the occurrence, development, and prognosis judgment of a variety of malignant tumors.