The relationship of melatonin (MT) level, oxidative stress and inflammatory status with osteoporosis in the maintenance hemodialysis (MHD) of chronic renal failure was investigated. Ninety-four patients with chronic renal failure treated in Dezhou People's Hospital (Dezhoo, China) and receiving MHD for more than 3 months from May to April 2017 were selected and divided into the osteoporosis group (observation group, n=49) and the non-osteoporosis group (control group, n=45) based on whether osteoporosis was involved. The serum advanced oxidation protein products (AOPP), MT level and inflammatory factors [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-1] in patients were detected via enzyme-linked immunosorbent assay (ELISA). Moreover, the malondialdehyde (MDA) level in serum was detected via thibabituric acid (TBA) assay and the spinal bone mineral density (BMD) was detected using the total BMD testing instrument, followed by correlation analysis. The MT level in observation group was significantly lower than that in control group, but the levels of AOPP and MDA were significantly higher than those in control group (P<0.05). The levels of inflammatory factors (TNF-α, IL-6 and IL-1) in observation group were obviously higher than those in the control group (P<0.05). Besides, the spinal BMD and T-value in observation group were significantly lower than those in the control group (P<0.05). Pearson's correlation analysis showed that AOPP, MDA, TNF-α, IL-6 and IL-1 levels were negatively correlated with BMD, but MT was positively correlated with BMD (P<0.05). Osteoporosis occurs easily in MHD patients; oxidative stress and inflammatory degree are negatively correlated with osteoporosis, but MT is positively correlated with osteoporosis.