The FAS–FASL system plays crucial role in counterattack of cancer cell against immune system. This study examined the effects of FAS (−1377G/A and −670A/G) and FASL (−844T/C and 7896G/C) polymorphisms on breast cancer risk and apoptosis of T lymphocytes. The effect on breast cancer risk was determined by case–control analysis of 840 patients and 840 controls. The effects on T-lymphocyte apoptosis were determined by activation-induced cell death (AICD) of T cells ex vivo and by analyzing apoptotic tumor-infiltrating lymphocytes (TILs) in breast cancer tissue. We found moderately increased risk associated with FAS −1377AG [odds ratio (OR), 1.29; 95% confidence interval (CI), 1.05–1.59] and −1377AA (OR, 1.36; 95% CI, 1.01–1.82) genotypes compared with the −1377GG genotype and decreased risk associated with FASL −844CT (OR, 0.76; 95% CI, 0.62–0.94) and −844TT (OR, 0.66; 95% CI, 0.43–1.00) genotypes compared with the −844CC genotype. T lymphocytes with the FASL −844CC genotype had heightened FASL expression that is associated with increased AICD of the T cells stimulated by MCF-7 cells or phytohemagglutinin compared with the FASL −844TT genotype (10.38 ± 4.09% and 24.29 ± 1.50% versus 6.03 ± 0.41% and 17.96 ± 3.66%; P < 0.05 and 0.001). Breast cancer patients with the FASL −844CC genotype had higher apoptotic TILs in their cancer tissues than those with the FASL −844TT genotype (33.7 ± 1.2% versus 19.1 ± 2.0%; P = 0.007). These findings indicate that functional polymorphisms in FAS and FASL contribute to increased apoptosis of tumor infiltration lymphocytes and risk of breast cancer.