Objective To explore the relationship between the levels of serum mucin 1 （MuC1）， type Ⅰprocollagen N-terminal propeptide （PINP）， and free light chain （sFLC） in patients with multiple myeloma and their clinical staging， immunophenotyping， and to evaluate their predictive value for prognosis. Methods A total of 220 patients with multiple myeloma admitted to Wuwei People's Hospital between July 2020 and May 2024 were selected as the case group. All patients were clearly staged according to the International Staging System （ISS）： stage Ⅰ （26 cases）， stage Ⅱ （82 cases）， and stage Ⅲ （112 cases）. Based on immunophenotyping， they were further classified into immunoglobulin （Ig） A type （52 cases）， IgG type （96 cases）， light chain type （47 cases）， and non-secreting type （25 cases）. Moreover， according to the patients' prognosis within 12 months of treatment follow-up， they were divided into the poor prognosis group （55 cases） and the good prognosis group （165 cases）. A control group of 220 healthy individuals who underwent physical examinations during the same period was also selected at a ratio of 1∶1. The clinical data and levels of serum MuC1， PINP， and sFLC （including sFLC-κ and sFLC-λ for horizontal κ and λ light chains） were compared between the case group and the control group. The levels of serum MuC1， PINP， and sFLC were also compared among patients with different clinical stages， immunophenotypes， and prognoses. The predictive value of serum MuC1， PINP， and sFLC levels for the prognosis of multiple myeloma patients was evaluated by receiver operating characteristic （ROC） curve analysis. Results The levels of serum MuC1， sFLC-κ， and sFLC-λ in the case group were significantly higher than those in the control group， whereas the level of serum PINP was significantly lower than that in the control group （P < 0.05）. In patients， the levels of serum MuC1， sFLC-κ， and sFLC-λ in stage Ⅲ were significantly higher than those in stages Ⅰ and Ⅱ， and the levels in stage Ⅱ were significantly higher than those in stage Ⅰ （P < 0.05）. Conversely， the level of serum PINP in stage Ⅲ was significantly lower than that in stages Ⅰ and Ⅱ， and the level in stage Ⅱ was significantly lower than that in stage Ⅰ （P < 0.05）. In terms of immunoglobulin types， the levels of serum MuC1， sFLC-κ， and sFLC-λ in patients with IgG type were significantly higher than those in patients with IgA type， light chain type， and non-secreting type， while the level of serum PINP was significantly lower than that in patients with these types （P < 0.05）. Regarding prognosis， the levels of serum MuC1， sFLC-κ， and sFLC-λ in the poor prognosis group were significantly higher than those in the good prognosis group， while the level of serum PINP was significantly lower than that in the good prognosis group （P < 0.05）. When defining poor prognosis as positive and good prognosis as negative， the area under the curve （AUC） for predicting the prognosis of multiple myeloma patients using serum MuC1， PINP， sFLC-κ， sFLC-λ， and their combined detection were 0.765， 0.665， 0.753， 0.710， and 0.914， respectively. The diagnostic sensitivities were 72.73%， 69.09%， 72.73%， 65.45%， and 87.27%， respectively， and the specificities were 69.70%， 62.42%， 72.12%， 73.33%， and 85.45%， respectively. Among these， the combined detection had the highest AUC （P < 0.05）. Conclusion The expressions of serum MuC1， PINP， and sFLC were associated with the occurrence， progression， and immunophenotyping of multiple myeloma， and they had high predictive value for patient prognosis. The combined detection of these four markers had the highest predictive value.