Abstract: Objective Treatment of multiple myeloma with bortezomib-based regimens has made significant progress in the prognosis of patients. In the past, the use of intravenous administration has been limited to a certain extent, but its side effects have limited its application. Methods In this study, 45 patients with multiple myeloma were analyzed retrospectively. Bortezomib was injected subcutaneously (SC group) or intravenously (IV group) at the dose of 1.3 mg/m², on D1, D4, D8, and D11. The efficacy and adverse reactions of the two ways of administration were observed. At the same time, the influencing factors of prognosis were analyzed. Results There was no significant difference in OS (P=0.163, P>0.05) and PFS (P=0.688, P>0.05) between the two groups. There was no significant difference in clinical efficacy between the two groups (P=0.760, P > 0.05). The incidence of peripheral neuropathy adverse reactions between the two groups was statistically significant (P=0.030, P<0.05). No statistically significant difference between the two groups was observed regarding other adverse reactions (P＞0.05). Conclusions The clinical efficacy of two routes of administration of bortezomib is similar, but the incidence of adverse reactions of subcutaneous bortezomib is lower than that of intravenous bortezomib.