【Objective】 To investigate the population data of human immunodeficiency virus (HIV) infections among voluntary blood donors in Guangzhou between 2012 and 2022, and analyze its characteristics and trends, so as to provide valuable data for formulating targeted prevention and ensuring blood safety. 【Methods】 Voluntary blood donors samples from 2012 to 2022 were screened for p24 antigen and anti-HIV by two ELISA diagnostic kits and HIV RNA by nucleic acid test(NAT). The reactive blood samples were sent to the Disease Control and Prevention Center of Guangzhou for anti-HIV confirmatory test by Western blot. The population characteristics of blood donors with confirmed-positive HIV were subsequently analyzed. 【Results】 There were a total of 3 351 596 blood samples from voluntary blood donors in Guangzhou from 2012 to 2022, of which 708 samples were confirmed-positive of anti-HIV, with a total positive rate of 21.12/100 000, showing a decreasing trend (P<0.05). 1) The positive rates of age groups from high to low were 25-34 year old group, 35-44 year old group, 18-24 year old group, and≥45 year old group. The differences among various groups are statistically significant; 2) The anti-HIV positive rate of first-time blood donors (39.23/100 000) was significantly higher than that of repeat blood donors (10.78/100 000) (P<0.05); 3) The anti-HIV positive rate of male blood donors was 30.45/100 000, which was significantly higher than that of female blood donors (3.46/100 000); 4) The anti-HIV positive rate of individual blood donors (32.18/100 000) was higher than that of group blood donors (9.10/100 000) (P<0.05). 【Conclusion】 From 2012 to 2022, the confirmed-positive rate of anti-HIV among voluntary blood donors in Guangzhou showed a downward trend, which was significantly correlated with the implementation of voluntary blood donation and AIDS prevention policies. Young blood donors are of high risk of HIV, and it is necessary to enhance publicity and education on AIDS prevention through multiple channels among young population. Given that the anti-HIV positive rate of first-time blood donors is much higher than that of repeat blood donors, it is recommended to further optimize the health consultation and physical examination process before blood donation, and take multiple measures to screen high-risk behavior groups. Besides, more efforts should be made to promote publicity and education on AIDS prevention among regular blood donors. It is also important to recruit blood donors from low-risk groups and inform the donors about confidential unit exclusion.