Recent studies indicated to the immune disturbances in cancer patients in comparison with healthy individuals. Several studies suggested that individuals with external locus of control (E-LOC) have more symptoms of depression. Other studies indicated to the effective role of psychological status on the immune system. The association between E-LOC and immunity in cancer patients it is not clear. Study the relation between Rotter internal-external locus of control (I-E LOC) and God health locus of control (GHLC) and interleukin-6 (IL-6) in breast cancer patients. The study included hundred breast cancer patients and fifty healthy controls. Patients and participators responded to I-E LOC and GHLC questionnaires. Peripheral blood samples were collected to measure gene expression of IL-6 by using real time PCR. Breast cancer patients showed higher GHLC which was associated with higher level of IL-6 as compared to control subjects. By contrast, a significant inverse correlation between GHLC and IL-6 was found. However, there was no relationship between I-E LOC and IL-6. The results suggest no significant effect of LOC belief according to life on immune response against cancer, but high GHLC belief correlate with decreased IL-6. Further studies on the relations between other types of LOC and immune response in breast cancer is recommended.