Across clinical trials, the expansion and persistence of adoptively transferred T cells has correlated with superior patient outcomes. Thus, translatable strategies which can engineer enhanced survivability and durability into transferred T cells remains a critical goal. Using the TCGA database, we found that a significant fraction of both hematologic and solid tumors overexpress FASLG, the gene encoding the canonical apoptosis-inducing ligand FASLG. Further, we found that FAS, the receptor for FASLG, was highly expressed by T-cell subsets isolated from patients with melanoma and diffuse large B-cell lymphoma prior to engineering for adoptive immunotherapy. We therefore hypothesized that a cognate interaction between FASL and FAS on adoptively transferred T cells might limit T cell expansion, persistence and antitumor efficacy. We generated a series of retrovirally-encoded Fas constructs with the aim of ‘insulating’ engineered T cells from the death-inducing functions of FASLG. These constructs included a Fas variant bearing a point mutation (FasI264N) limiting FADD binding and a truncation variant missing the majority of the death domain (FasΔDD). Introduction of either FasI264N or FasΔDD into Fas-competent primary mouse or human T cells prevented FasL-induced apoptosis. Whereas T cells engineered with an empty construct underwent apoptosis when co-cultured with tumor cells, this process was prevented in T cells engineered with either FasI264N or FasΔDD. Relative to empty vector controls, T cells engineered with either FasI264N or FasΔDD exhibited enhanced persistence and engraftment within the tumor following transfer in vivo. This enhanced survival was in turn correlated with superior tumor regression in a B16 melanoma model. In long term engraftment experiments, neither the FasI264N nor FasΔDD-engineered T cells clonally expanded or caused an ALPS syndrome. Thus, ‘insulating’ T cells from the negative influence of FasL is a translatable strategy resulting in superior T cell persistence and enhanced antitumor efficacy following adoptive T cell transfer.