This study aimed to investigate the influence of FGFR3 gene mutations on the clinical characteristics and prognosis of patients with newly diagnosed multiple myeloma (NDMM) . A total of 198 patients with NDMM admitted to the Department of Hematology in Jiangsu Province Hospital between January 2016 and February 2023 were retrospectively analyzed. Next-generation sequencing and cytoplasmic light chain immunofluorescence with fluorescence in situ hybridization were performed for all patients. The prognostic significance of FGFR3 mutation and clinical features were analyzed using the Log-rank test and Cox proportional hazards model. Among 198 patients, 28 carried the FGFR3 gene mutation. These patients had significantly lower serum albumin levels, higher β(2)-microglobulin levels, advanced Revised International Staging System stages, more frequent occurrence of t (4;14) , and shorter median progression-free survival (PFS) time (28 months 33 months, =0.024) and overall survival (OS) time (54 months undefined, =0.028) than patients without FGFR3 mutation. Additionally, patients carrying either FGFR3 mutation or t (4;14) had lower PFS (30 months 38 months, =0.012) and OS (54 months undefined, =0.017) than those without. The Cox proportional hazards model identified FGFR3 mutation as an independent risk factor for PFS and OS. FGFR3 gene mutation was an unfavorable independent prognostic predictor for NDMM.