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In Egypt, there is no legislation for deceased donor transplant; therefore, programs provide living donation only. One possible barrier against living liver donation may be the attitude of the health-care professional. This study aimed to (1) assess the level of knowledge and attitude toward liver donation and transplantation among health-care professional in an University Hospital in Upper Egypt and (2) analyze the variables that affect such an attitude.This was a cross-sectional survey study with 300 health-care professionals.The mean (standard deviation) age was 27.4 (5.3) years. Two hundred (66.7%) were females, and 257 (85.7%) were Muslims. A total of 222 (74%) were residents in University Hospitals. Of the sample, 104 (34.7%) would donate a living liver part, 122 (40.7%) discussed the matter of organ donation and transplantation with their family, and 134 (44.7%) did not discuss this issue with their family. About 40% knew the attitude of their religion toward organ donation. Most (94.7%) health professionals were <40 years and did not know the attitude of their religion toward this issue. Single persons had more correct information regarding living organ donation and transplantation. More Muslims know the attitude of their religion toward living organ donation and transplantation.Independent predictors of accepting living liver donation are being younger, knowledge of religion attitude, and media coverage satisfaction (P = 0.006, odd ratio [OR] = 0.2; P = 0.000, OR = 0.39; and P = 0.016; OR = 0.38).