Background Accurate diagnosis of tumors is crucial for patient treatment and prognosis. Special staining and immunohistochemistry staining each has its own advantages, but they still have limitations when used individually. Combining the two may provide more comprehensive and accurate diagnostic information; however, the clinical value of this approach requires systematic evaluation. Objective To explore the application value of special staining combined with immunohistochemistry staining in tumor diagnosis and to evaluate its diagnostic efficacy. Methods A total of 80 tumor patients treated at Zhengzhou Yihe Hospital from January 2021 to December 2023 were selected, including 25 cases of metastatic tumors, 20 cases of primary liver cancer, 15 cases of hemangiomas, and 20 cases of intrahepatic cholangiocarcinomas. Tissue samples from the patients were subjected to immunohistochemical staining, Masson staining, PAS staining, and Congo red staining. Using pathological diagnosis as the gold standard, the diagnostic efficacy of various staining methods was compared, including accuracy, sensitivity, specificity, positive predictive value, and negative predictive value. The diagnostic efficacy of each staining method was analyzed using ROC curves. Results The ROC curve area for the combination of special staining and immunohistochemical staining was the largest (0.943), indicating the highest diagnostic efficacy. This combined method showed an accuracy of 97.50%, a sensitivity of 98.57%, and a specificity of 90.00%, all of which were significantly higher than those of the individual staining methods (P<0.05). When immunohistochemistry staining was used alone, the accuracy was 92.50%, the sensitivity was 95.71%, and the specificity was 70.00%. The accuracy of Masson staining, PAS staining, and Congo red staining was 82.50%, 87.50% and 80.00% respectively, all lower than that of the combined staining method (P<0.05). Conclusion The combination of special staining and immunohistochemistry staining has high application value in tumor diagnosis, significantly improving diagnostic accuracy, sensitivity and specificity, superior to single staining method. This combined technique can provide more reliable evidence for clinical tumor diagnosis.