In our study, we successfully developed a prognostic signature comprising 16 SPP1+ TAMs-related genes (FCGR2B, CAPNS1, C11orf58, NDUFA8, CD37, SRI, KYNU, UBE2I, TFPT, PSMC6, CALM3, DDT, NME1, RABAC1, GTF2H5, CDC42), which demonstrated the potential to predict OS in patients with HCC. This evidence concerns the gene NDUFA8 and hepatocellular carcinoma.