Objective To analyze the effect of recombinant human erythropoietin combined with roxadustat in the treatment of renal anemia in patients with multiple myeloma (MM).Methods A total of 84 patients with MM renal anemia treated in our hospital between January 2020 and December 2021 were selected, and they were randomly divided into observation group (n=42) and control group (n=42). Both groups were given conventional chemotherapy. The control group was given recombinant human erythropoietin, and the observation group was given recombinant human erythropoietin combined with roxadustat. The treatment effects, improvement of life quality, and the incidence of adverse reactions were compared between the two groups. The hemoglobin (Hb), erythropoietin (EPO), hypoxia-inducible factor-1α (HIF-1α), serum creatinine (Scr), urea nitrogen (BUN), serum transferrin saturation (TSAT), serum iron ( SI), total iron-binding capacity (TIBF), interleukin-1β (IL-1β), IL-6 were also detected before treatment and after the 1st and the 3rd courses of treatment.Results The treatment effect of the observation group was better than that of the control group (P<0.05). Scores of physiological field, psychological field, environmental field and social relation field were significantly increased in two groups after the 1st and the 3rd courses of treatment (P<0.05), and those of the observation group was higher than those of the control group after the 1st and the 3rd courses of treatment (P<0.05). The levels of Hb, EPO, TSAT, SI and TIBF after the 1st and the 3rd course of treatment were significantly increased, and the observation group had higher levels of the above indicators than the control group (P<0.05). The levels of Scr, BUN, IL-1β and IL-6 in the two groups were decreased after the 1st and the 3rd courses of treatment, and the observation group had lower levels than the control group (P<0.05). The levels of HIF-1α in the observation group were decreased after the 1st and the 3rd courses of treatment, and were also lower than in the control group (P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P>0.05).Conclusion Recombinant human erythropoietin combined with roxadustat has a significant effect in the treatment of MM patients with renal anemia. It can improve the level of EPO, inhibit the inflammatory response, correct iron metabolism, and achieve the purpose of improving the quality of life of anemia patients. It can also reduce the level of HIF-1α and help to promote the recovery of renal function.