Background: Well-motivated staff nurses with high levels of self-efficacy are valued assets for organizational success. Aim of study: to assess motivation and its influence on staff nurses' self-‎efficacy. Subjects and Methods: This cross-sectional study was carried out at Ain-Shams University Hospital on a convenience sample of 169 staff nurses. Data were collected using the motivational factors questionnaire and the General Self-Efficacy Scale‎. Results: Staff nurses' age was 17-59 years, 46.2% males, and 37.3% with bachelor's degree. Overall, 53.3% had high total motivation, and 69.8% had high total self-efficacy. The scores of motivation and self-efficacy had significant positive correlation (r=0.190). In multivariate analysis, Age was a positive predictor of motivation score, while qualification and experience years were negative predictors. Being married was a positive predictor of the self-efficacy score. Conclusion and Recommendations: Staff nurses' self-efficacy and motivation are positively correlated. More efforts are needed to improve staff nurses' motivation and self-efficacy using innovative educational approaches. Further research is proposed to investigate the effect of interventions improving work motivation on self-efficacy.