Objective To discuss the correlation between serum fibroblast growth factor receptor 2 FGFR2 cellular communication network 1 CCN1 and prognosis in patients with multiple myeloma MM . Method A total of 104 newly diagnosed MM patients who received treatment in Hebei PetroChina Central Hospital from September 2020 to January 2022 were selected as the study group and 106 healthy people of the same age who passed the health examination test in our hospital were selected as the control group. According to the follow-up results of prognosis patients in the study group were classified into a survival group of 62 cases and a death group of 42 cases. ELISA method was used to detect the serum FGFR2 and CCN1 in patients. Pearson analysis analyzed the correlation between serum FGFR2 and CCN1 levels and age and ISS stage of patients. The risk factors of death in MM patients were analyzed by multivariate Cox regression. ROC curves were used to analyze the diagnostic value of serum FGFR2 and CCN1 levels in the mortality of MM patients. The Kaplan-Meier method was used to analyze the relationship between serum FGFR2 and CCN1 levels and the three-year survival rate of MM patients. Result For the control group the study group had clearly higher serum FGFR2 and clearly higher CCN1 P< 0. 05 . For the survival group the death group had clearly higher serum FGFR2 and clearly higher CCN1 P< 0. 05 . The differences in age and ISS staging between the survival group and the death group were statistically clear P< 0. 05 . Serum FGFR2 level was positively correlated with ISS stage and serum CCN1 level was negatively correlated with ISS stage P< 0. 05 . FGFR2 CCN1 age and ISS stage were independent risk factors for mortality in patients with MM P<0. 05 . The joint of serum FGFR2 and CCN1 had an AUC of 0. 953 for diagnosing death in MM patients. The joint diagnosis was superior to individual diagnosis Z= 3. 513 3. 237 P< 0. 05 . The three-year survival rate of patients with high serum FGFR2 was lower than that of patients with low serum FGFR2 and the three-year survival rate of patients with low serum CCN1 was lower than that of patients with high serum CCN1 P < 0. 05 . Conclusion Serum FGFR2 is upregulated and CCN1 is downregulated in MM patients they are associated with prognosis. The joint of the two has certain value in diagnosing the death of MM patients.