Although alterations in calcium levels are known to play an important role in a variety of physiological processes, only in past few years has the role of calcium signaling in regulation of apoptosis been well recognized. It has been shown that apoptotic stimuli provoke rapid elevation of cytosolic calcium concentration, which in turn orchestrates the release and activation of multiple pro-apoptotic factors. Our previous results in T cells demonstrated that Fas-mediated apoptosis requires calcium release, which was dependent upon phospholipase C-γ1 (PLC-γ1) activation and calcium release from inositol 1,4,5-trisphosphate receptor (IP3R) channels. Here, we show that PLC-γ1 activation after Fas receptor ligation requires canonical components of the T cell receptor complex. Specifically, the active form of the Src family tyrosine kinase Lck and PLC-γ1 become associated with the death-inducing signaling complex (DISC) in a stimulus-dependent manner. We found that Lck activates PLC-γ1 indirectly via Zap70 tyrosine kinase and other members of the T cell receptor signaling pathway. Moreover, in absence of a functional T cell receptor complex, Fas stimulation failed to induce calcium release. This led to significantly inhibited effector caspase activation and delayed cell death. These findings strongly suggest a vital interplay between Fas and the T cell receptor complex, which has significant implications for T cell regulation.