La2O3 nanofibers was synthesized through electrospinning and heat treatment process. The phase structure, morphology and antibacterial performance were characterized by SEM, TEM, XRD, XPS and BET. The result shows that La2O3 nanofibers possessed high length–diameter ratio, uniform morphology and pure phase. The La2O3 nanofibers have an excellent germicidal effect against the high-risk human pathogen Escherichia coli O157. More than 95% inactivation rate of hige concentration bacterial (107 CFU/L) is achieved in 100 minutes by low addition of La2O3 nanofibers (200 mg/L) and no E. coil recovery was detected in following three days. Furthermore, La2O3 nanofibers shows high efficient bactericidal performance against Acinetobacter baumannii and P.aeruginosa, demonstrating its potential application as efficient and broad-spectrum antimicrobial material.