Background: Chinese herbal medicine (CHM) is used widely to treat various diseases, including cancer. However, effective herb pairs for treating specific cancer types have so far not been identified. Here, we aimed to calculate the survival benefits of herb pairs by cluster analysis, association rules, and survival evaluation in patients with esophageal cancer (EC) treated with CHM. Patients and Methods: 59 patients with EC who received 176 prescriptions including 178 types of herbs were enrolled into the study. The herb pairs were identified by both cluster analysis and association rules. Overall survival (OS) was estimated by the Kaplan-Meier method. Results: Eight groups of herb pairs were identified by cluster analysis, and 4 groups of herb pairs were identified by association rules. Of these, 3 groups of herb pairs were identified by both methods. OS estimation showed that the pair of chicken gizzard-membrane/Astragalus was associated with improved survival in patients with EC treated with CHM. Conclusion: Patients who received prescriptions containing the pair of chicken gizzard-membrane and Astragalus had improved OS compared with patients who received prescriptions lacking this pair.