Patient safety is a priority for implementation of the five important safety issues in hospital, because of patient safety issues related to the quality and image of the hospital it self.Therefore patient safety is the first priority to be implemented and it is related to the issue of the quality and image of the hospital.Objectivein this study was to determine the effect of Perception variables about Professionalism, Patients Safety Knowledge and motivation of nurses on the implementation of patient safety programs in the Inpatient Room of RSUD X Regional Hospital Semarang.Thisresearch methodwas quantitative observational analytic a cross sectional research with purposive sampling, and amount of respondent are 120.Obstain data was processes with SPSS Amos 24 software .The results showed that the perception variable about nursing professionalism (0.377) had the most positive and direct effect on the implementation of patient safety programs compared to the direct influence of patient safety knowledge (0.223) and patient safety motivation (0.266) patient safety implementation programs. This means that the increase in the implementation of patient safety programs is greatly influenced by the role of perception of nursing professionalism.