Objective: To assess the quality of life (QOL) and mental health of hemodialysis (HD) patients with infectious diseases, to analyze the related factors, and to provide evidence for improving the QOL of these patients and guiding the direction of clinical intervention. Methods: This case-control study investigated 107 HD patients (57 with and 50 without infectious diseases) using questionnaires, including the Brief Version of World Health Organization Quality of Life (WHOQOL-BREF), Kidney Disease Quality of Life, self-rating depression scale (SDS), self-rating anxiety scale (SAS), and social support rating scale (SSRS). The data were analyzed using independent t-test, analysis of variance, chi-square test, and multiple linear regression analysis. Results: The differences in general characteristics between HD patients with and without infectious diseases were not significant. The differences in age, dialysis time, education level, and marital status were significant among HD patients with different infectious diseases. The AIDS/HIV HD patients had lower scores in the fields of psychology, social relations, and the environment in the WHOQOL-BREF and in the psychological field of the KDQOL-36 compared with the other two subgroups (P < 0.05). The utilization of support score in SSRS was lower in HD patients with AIDS/HIV than in those with syphilis (P < 0.05). Multiple linear regression analysis demonstrated a decrease in the WHOQOL-BREF scores in the AIDS/HIV subgroup compared with the noninfectious, hepatitis, and syphilis subgroups. Conclusion: Compared with HD patients without infectious diseases, HD patients with infectious diseases (including hepatitis B/C virus, syphilis, and AIDS/HIV), especially those with AIDS/HIV, had a lower QOL, more serious negative emotions (depression and anxiety), and a greater difficulty in obtaining social support.