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Poly(amidoamine) dendrimer (PAMAM) is well known for its high efficiency as a drug 3 delivery vehicle. However, the intrinsic cytotoxicity and lack of a detectable signal to facilitate 4 tracking have impeded its practical applications. Herein, we have developed a novel label-free 5 fluorescent and biocompatible PAMAM derivative by simple surface modification of PAMAM 6 using acetaldehyde. The modified PAMAM possessed a strong green fluorescence, which was 7 generated by the C=N bonds of the resulting Schiff Bases via n-π* transition, while the intrinsic 8 cytotoxicity of PAMAM was simultaneously ameliorated. Through further PEGylation, the 9 fluorescent PAMAM demonstrated excellent intracellular tracking in human melanoma 10 SKMEL28 cells. In addition, our PEGylated fluorescent PAMAM derivative achieved 11 enhanced loading and delivery efficiency of the anticancer drug doxorubicin (DOX) compared 12 to the original PAMAM. Importantly, the accelerated kinetics of DOX-encapsulated 13 fluorescent PAMAM nanocomposites in an acidic environment facilitated intracellular drug 14 release, demonstrating comparable cytotoxicity to that of the free-form doxorubicin 15 hydrochloride (DOX•HCl) against melanoma cells. Overall, our label free fluorescent 16 PAMAM derivative offers a new opportunity of traceable and controlled delivery for DOX and 17 other drugs of potential clinical importance.