Abstract: Small RNAs are essential regulators for T cell development, differentiation and functions. However, it is hard to deliver small RNAs into primary T cells by conventional transfection methods. Here, we reported that amphiphilic PBA-grafted PEI1.8k (PEI-PBA) nanovector facilitates the primary T cell-targeted RNA delivery miRNAthrough recognition of sialic groups on cell membrane of the T lymphocytes. CCK-8 (cell counting kit-8) and CFSE (5, 6-carboxyfluorescein diacetate, succinimidyl ester) assay showed that the administration of PEI-PBA did not cause significant cell toxicity or abnormal proliferation. Meanwhile, the flowcytometry showed the average intake of miRNA was increased to 18.43% in the anti-CD3/CD28 activated CD3+ (cluster of differentiation 3) T lymphocytes by PEI-PBA in human, but not mouse. The results showed that PEI-PBA nano-system had effective delivery of small RNAs in human primary T cells without toxcity.