Objective: To investigate the effect of CD4-positive T lymphocyte expression rate on the pain control and prognosis of stage Ⅳ non-small cell lung cancer (NSCLC) patients with cancerous pain. Methods: The clinical data of 128 stage Ⅳ NSCLC patients with cancerous pain who were admitted to the Affiliated Cancer Hospital of Zhengzhou University from January to December 2020 were retrospectively analyzed, including 92 males and 36 females, with a male-to-female ratio of 23∶9 and an average age of (56±21) years old. The expression rate of CD4-positive T lymphocytes in peripheral blood was routinely detected on admission, and the expression rate of CD4-positive T lymphocytes ≥45% was defined as the CD4 high expression group, and0.05). The OS time and PFS time in the CD4 high expression group [M (Q1, Q3)] were 12.5 (8.1, 13.8) months and 8.5(3.1, 9.4) months, respectively, which were higher than those in the CD4 low expression group [8.6 (4.1, 12.9) months and 6.5 (2.1, 7.9) months, respectively] (all P<0.01). Cox multivariate analysis showed that high expression of CD4 was a protective factor affecting OS (HR=0.876, 95%CI: 1.224-6.641, P=0.004) and PFS (HR=0.675, 95%CI: 1.742-5.930, P=0.031) Conclusion: The stage Ⅳ NSCLC patients with cancerous pain and high expression of CD4-positive T lymphocytes have shorter pain control time, less morphine dosage, and longer OS and PFS time.