The problem of stability hinders the practical applications of nanomaterials. In this research, an innovative and simple synthetic method was developed for preparing ultrastable and multifunctional gold nanoclusters (Au NCs). HS-C-11-EG(6)-X is a class of molecules consisting of four components: a mercapto group (-SH), an alkyl chain (C-11), a short chain of polyethylene glycols (EG(6)) and a functional group (X, X = OH, COOH, NH2, GRGD, etc). The present work demonstrated the importance of using HS-C-11-EG(6)-X to prepare Au NCs with excellent properties and the role each component in this molecule played for synthesizing Au NCs. Au NCs with tunable surface functionalities were successfully synthesized and characterized. It was found that Au NC precursors had a fluorescent quantum yield of 0.4%; in contrast, after capping with HS-C-11-EG(6)-X, the quantum yield significantly increased to 1.3-2.6%. The HS-C-11-EG(6)-X capped Au NCs exhibited superior stability under various solution conditions (including extreme pH, high salt concentration, phosphate buffered saline and cell medium) for at least 6 months, even after conjugation with anticancer drug doxorubicin. Besides, we have also demonstrated that other commonly employed thiol-containing ligands failed to prepare stable fluorescent Au NCs. Moreover, the Au NCs showed negligible toxicity to A549 lung cancer cells up to 100 mu M, and the application of the ultrastable Au NCs for anticancer drug delivery has also been demonstrated. (C) 2015 Elsevier Inc. All rights reserved.