Ligand-protected gold nanoclusters (AuNCs) show promise for high performance in biological applications, such as imaging and therapeutics. The assembly of AuNCs with biological macromolecules represents a simple but effective approach to fine-tuning of material functionalities. Thus, these materials might enable intracellular applications of AuNCs. Herein, we prepared a new AuNC-based nanometric system through a self-assembly approach mediated by hydrophobic and electrostatic effects. We show that hydrophobic and electrostatic effects between fluorescent AuNCs with protamine and hyaluronic acid contribute to the formation of small nanocomposites with acceptable colloidal stability. More importantly, the AuNC-decorated nanocomposites show assembly enhanced emission and singlet oxygen generation. In vitro experiments showed that our nanocomposites labeled specific cells by targeting CD44 and induced cell death by producing singlet oxygen. Hence, our AuNC-decorated nanocomposites show great potential as theranostic fluorescent nanomaterials.