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Objective To detect the expression level of long non-coding carbonyl reductase 3 antisense RNA1(LncRNA CBR3-AS1) in the serum of patients with multiple myeloma and analyze its clinical significance. Methods This study included 100 patients with multiple myeloma who were first diagnosed in Shijiazhuang People's Hospital from January 2012 to March 2020 as the observation group, and 50 healthy people under the age of 65 who had taken physical examination as the control group. Fluorescence quantitative PCR technology was used to detect the relative expression level of LncRNA CBR3-AS1 in the serum of each group, the relationship between the expression level of serum LncRNA CBR3-AS1 and the clinical parameters of patients with multiple myeloma was analyzed and compared, Kaplan-Meier survival curve was used to analyze the relationship between the expression level of serum LncRNA CBR3-AS1 and the prognosis of patients with multiple myeloma, univariate and multivariate Cox regression were used to assess the factors that may affect the prognosis of patients with multiple myeloma. Results The relative expression level of LncRNA CBR3-AS1 in the serum of the observation group was significantly higher than that of the control group (P＜0.05); The relative expression level of LncRNA CBR3-AS1 in the serum of patients with multiple myeloma was related to clinical Durie-Salmon (D-S) staging and International Staging System (ISS) staging(P＜0.05); Kaplan-Meier survival curve showed that the survival rate of patients in the LncRNA CBR3-AS1 low expression group (78.0%) was significantly higher than that of the patients in the LncRNACBR3-AS1 high expression group (58.0%)(χ2=5.370, P＜0.05); Univariate analysis showed that clinical D-S staging (HR=2.159; 95% CI=1.323-3.524; P＜0.05), ISS staging(HR=1.746; 95% CI=1.091-2.794; P＜0.05) and serum LncRNA CBR3-AS1 expression (HR=1.975; 95% CI=1.210-0.224; P＜0.05) affected the prognosis of patients with multiple myeloma, multivariate Cox regression analysis showed that clinical D-S staging (HR=2.769; 95% CI=1.315-5.832; P＜0.05), ISS staging (HR=2.495; 95% CI=1.117-5.573; P＜0.05) and serum LncRNA CBR3-AS1 expression (HR=3.214; 95% CI=1.206-8.564; P＜0.05) were potential independent influencing factors to development of multiple myeloma. Conclusions Expression of CBR3-AS1 is increased in the serum of patients with multiple myeloma, which may relate to the prognosis of multiple myeloma.