Whole-body diffusion-weighted imaging (WB-DWI) is a method for evaluating bone marrow infiltration in multiple myeloma (MM). This study seeks to elucidate the correlation between the apparent diffusion coefficient (ADC) value and some selected clinical parameters.A total of 101 Chinese patients with MM who had undergone WB-DWI from May 2017 to May 2019 were enrolled in this study. The ADC values of the MM lesions and the clinical parameters were quantified at the first (baseline) visit and after four-course induction chemotherapy. Multiple linear regression and logistic analyses were carried out to find the implicit inherent relationships within the patients' data.The paired Wilcoxon test showed that the ADC values at the baseline visit (ADC0) were significantly lower than the values after four-course induction chemotherapy (ADC4 c) (p < 0.001), including different therapeutic responses. The Revised International Staging System (RISS) stage, type of MM, and β2-microglobulin (β2-MG) were predictors of clinically significant increases or decreases in the ADC values (p < 0.05). Multiple linear regression showed that the ADC0 was negatively associated with β2-MG (p < 0.001) and immunoglobulin heavy chain gene rearrangement (p = 0.012), while the RISS Stage III (p = 0.001), type IgG λ (p = 0.005), and albumin were negatively associated with ADC4 c (p = 0.010). The impacts of the therapeutic response were associated with ADC0 and immunoglobulin heavy chain gene rearrangement (p < 0.001).The ADC values of WB-DWI may be associated with clinical parameters of MM including the fluorescence in situ hybridization result, and may be useful in the prognosis of patients with MM.ChiCTR2000029587.