Cases of medical errors in health care services are serious problems. In Indonesia, the incidence of work accidents still often afflicts nurses in hospitals. The prevalence of patient safety is still high. The research aimed to analyze the factors that affected nurse performance in the application of the patient safety system at the hospital. The sampling technique employed a total sampling of 40 people. Data analysis functioned the Partial Least Square. The results shew: a) The knowledge influenced on the nurse performance and the work-life quality, b) The attitude of nurses affected the quality of work-life, but did not affect performance. The knowledge was the most robust variable affected performance. Conclusion: to improve nurse performance, a hospital should enhance the knowledge, attitudes, and nurse quality work of life.Kasus kesalahan medis dalam layanan perawatan kesehatan adalah masalah serius. Di Indonesia, insiden kecelakaan kerja masih sering menimpa perawat di rumah sakit. Prevalensi keselamatan pasien masih tinggi. Penelitian ini bertujuan untuk menganalisis faktor-faktor yang mempengaruhi kinerja perawat dalam penerapan sistem keselamatan pasien di rumah sakit. Teknik pengambilan sampel menggunakan total sampling 40 orang. Analisis data menggunakan Partial Least Square. Hasil menunjukkan: a) Pengetahuan mempengaruhi kinerja perawat dan kualitas kehidupan kerja, b) Sikap perawat mempengaruhi kualitas kehidupan kerja, tetapi tidak mempengaruhi kinerja. Pengetahuan adalah variabel yang paling kuat mempengaruhi kinerja. Kesimpulan: untuk meningkatkan kinerja perawat, rumah sakit harus meningkatkan pengetahuan, sikap, dan kualitas kerja perawat.