Zinc-Selenium (Zn-Se) alloys are promising biodegradable hard-tissue implant materials, particularly due to Se's efficacy in both preventing and treating cancer. However, the difficulty in alloying Zn with Se and the processing softening of Zn alloys seriously hinder the clinical application of Zn-Se alloys. Here, we report on the successful preparation of a Zn-4Cu-2Se alloy using casting and hot rolling, and its extraordinarily effective biocompatibility and antibacterial and anti-tumor capabilities. The microstructural compositions of the Zn-4Cu-2Se alloy prominently featured an η-Zn matrix and the intermetallic phases of ε-CuZn5 and ZnSe. The hot-rolled Zn-4Cu-2Se alloy demonstrated significant work-hardening behavior under tensile deformation and revealed a yield strength of 215±3 MPa, tensile strength of 234±2 MPa, and fracture strain of 12.1±0.2%, along with a moderate degradation rate of approximately 56.2±0.3 μm/year in Hanks' solution, meeting the benchmark mechanical and degradation properties for biodegradable orthopedic-implant materials. Furthermore, the hot-rolled Zn-4Cu-2Se alloy demonstrated markedly effective antibacterial capacity against S. aureus and anti-tumor activity against osteosarcoma MG63 cells, and profound biocompatibility and osteogenic capacity toward pre-osteoblast MC3T3-E1 cells. Overall, the hot-rolled Zn-4Cu-2Se alloy holds great promise for orthopedic applications owing to its unique integration of work-hardening behavior and biofunctionalities. STATEMENT OF SIGNIFICANCE: This work reports on the extraordinarily effective biocompatibility and antibacterial and antitumor capabilities of a hot-rolled Zn-4Cu-2Se alloy. The alloy demonstrated significant work-hardening behavior under tensile deformation, with a yield strength of ∼215 MPa, ultimate tensile strength of ∼234 MPa, elongation of ∼12.1%, and a moderate degradation rate of approximately 56.2 μm/year. Moreover, the alloy showed markedly effective antibacterial ability against S. aureus and antitumor activity against MG63 osteosarcoma cells, and significant biocompatibility and osteogenicity toward pre-osteoblast MC3T3-E1 cells. This Zn-4Cu-2Se alloy is promising for orthopedic applications owing to its unique combination of work-hardening behavior and biofunctional properties.