Objective To investigate the expression of serum homeobox C6(HOXC6),C-C motif chemokine ligand 18(CCL18),and soluble CD86(sCD86)in multiple myeloma patients and their correlation with prognosis.Methods Totally 110 patients with multiple myeloma accepted by our hospital from January 2020 to September 2023 were regarded as research group and followed up for one year.They were assigned into a good prognosis group(n=69)and a poor prognosis group(n=41),according to prognositic outcome.Additionally,135 healthy people who underwent physical checkups were recruited as control group.qRT-PCR was used to determine the relative expression of serum HOXC6 mRNA;ELISA was used to measure serum CCL18 and sCD86;K-M method was used to analyze the relationship of serum HOXC6,CCL18,sCD86 with overall survival(OS)and progression-free survival(PFS)in multiple myeloma patients.Receiver operating characteristic(ROC)curves were plotted to analyze the prognostic value of serum HOXC6,CCL18 and sCD86 in patients with multiple myeloma;COX regression model was used to analyze the factors influencing the prognosis of patients with multiple myeloma.Results Compared with the control group,the research group had higher levels of serum HOXC6,CCL18 and sCD86(P＜0.05).The median OS time and median PFS of patients with high and low expression of HOXC6,CCL18 and sCD86 were significantly different(P＜0.05).The poor prognosis group had a higher proportion of ISS stage Ⅲ,and higher levels of serum HOXC6,CCL18,sCD86 than those of good prognosis group(P＜0.05).The AUC value of combination of serum HOXC6,CCL18 and sCD86 for predicting poor prognosis in multiple myeloma patients was greater than that of serum HOXC6,CCL18 or sCD86 alone(P＜0.05).Conclusion The combination of serum HOXC6,CCL18 and sCD86 has a high predictive power for poor prognosis in patients with multiple myeloma,and all three are risk factors for poor prognosis.