Gold nanoclusters (AuNCs) with an ultrasmall size showed potential application in photodynamic therapy (PDT), but short circulation and weak tumor retention restricted their PDT performance. Herein, bovine serum albumin (BSA) nanospheres with good biocompatibility were used to encapsulate AuNCs, by which the stable and biocompatible AuNCs@BSA nanoprobes were synthesized to boost PDT performance. The results showed that ultrasmall AuNCs with a size of 1.5 nm were encapsulated in BSA nanospheres, and the prepared AuNCs@BSA nanoparticles with an average size of 120 nm have high colloid stability and enhanced fluorescence emission. Compared with single AuNCs, AuNCs@BSA possessed higher singlet oxygen yield, which increased from 34.5% to 45.5%. Moreover, AuNCs@BSA showed lower cytotoxicity and stronger cellular uptake, by which the cell viability was reduced to 20.6% and 4T1 tumor completely disappeared, compared with 47.5% cell viability and tumor recurrence of single AuNCs. The results demonstrated that the prepared AuNCs@BSA nanoprobes possessed good biocompatibility and boosted PDT performance and will be potential highly efficient PDT nanoprobes owing to their safety and reliability.