The invention provides a transgenic lymphocyte, a construct, and a therapeutic composition for treating cancer. The cell checkpoint of the transgenic lymphocyte is silenced; and the transgenic lymphocyte expresses a non-function EGFR and a chimeric antigen receptor. The chimeric antigen receptor comprises an extracellular region, which comprises the heavy-chain variable region and the light-chainvariable region of a single-chain antibody that specifically recognizes the antigen mesothelin; a transmembrane region, which is connected with the extracellular region and embedded into the cell membrane of a T lymphocyte; and an intracellular region, which is connected with the transmembrane region and comprises the intracellular segment of CD28 or 4-1BB and a CD3 zeta chain. The transgenic lymphocyte has the characteristic of resisting tumor cell-mediated immunosuppression, is substantially strengthened in the ability of killing tumor cells, particularly has remarkable directional killing effect on tumors with high expression of mesothelin, and has high safety.