Objective To investigate the proportion of CD4+ T cells, which express the granzyme A, B and perforin, in peripheral blood of patients with primary hepatocellular carcinoma (PHCC), and explore the correlation between CD4+ T and the course of PHCC. Methods Peripheral blood samples were obtained from 99 PHCC patients, 28 chronic hepatitis B (CHB) patients, and 40 healthy subjects (served as control), and CD4+ cytotoxic T cells in peripheral blood were quantitatively analyzed with flow cytometry. The difference of proportion of CD4+ T cells between early (n=29), intermediate (n=36) and progressive (n=34) stage of PHCC patients was also analyzed. Results It was revealed that the proportions of granzyme A+ CD4+ CTL, granzyme B+ CD4+ CTL and perforin+ CD4+ CTL were significantly higher in PHCC patients (15.38%±10.36%, 11.10%±8.43% and 7.42%±7.26%) compared with those in CHB patients (9.10%±5.80%, 6.16%±6.04% and 2.95%±3.34%) and healthy controls (10.25%±5.62%, 6.82%±6.12% and 3.14%±3.60%, P<0.05), but no statistical difference of the values existed between CHB patients and healthy controls. The proportions of granzyme A+ CD4+ CTL in early, intermediate and progressive stage of PHCC patients were 21.26%±12.61%, 14.54%±7.11% and 11.24%±9.04%, and of granzyme B+ CD4+ CTL were 15.35%±10.30%, 10.71%±6.06% and 7.90%±7.44%, and of perforin+ CD4+ CTL were 11.82%±9.17%, 7.16%±5.03% and 5.22%±6.58%, respectively. The proportions of CD4+ CTL declined along with the deterioration of PHCC. Conclusion The proportion of CD4+ CTL increases in the peripheral blood of PHCC patients, but it declines along with the deterioration of disease, implying that the CD4+ cytotoxic T may be closely associated with the deterioration of PHCC.