Fatty acid-binding protein 5 ( FABP5), which participates in mediating the biological properties of tumor cells, has been recognized in several neoplasms. The present study aims to investigate FABP5 transcriptional expression profiles, reveal its underlying biological interaction networks and define its prognostic value in uveal melanoma (UVM). A total of 80 patients with UVM and their RNA-sequence data, available from The Cancer Genome Atlas (TCGA) database, was analyzed. A differential transcriptional expression profile was obtained from TCGA and the Oncomine databases. The survival benefits were analyzed using the Kaplan-Meier method and log-rank test. The correlation between FABP5 expression and immune infiltration level was analyzed using the Tumor Immune Estimation Resource database. Functional enrichment analyses using Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and signaling hallmarks were utilized to describe the biological process, molecular functions, cellular component and significantly involved pathways. The elevated transcriptional expression of FABP5 was significantly associated with shorter overall survival (OS) and worse progression-free survival (PFS) times in patients with UVM (P<0.001). Moreover, FABP5 expression was significantly and positively correlated with tumor purity and CD8 + T cells and was negatively correlated with the infiltrating levels of CD4 + T cells and neutrophils. Gene Set Enrichment Analysis was performed to obtain 100 significantly associated genes of FABP5 and FABP5 was found to be critical in several hallmark pathways, including allograft rejection, complement, interleukin-6/Janus kinase-STAT3 signaling, interferon γ response, inflammatory response and tumor necrosis factor α signaling via NFκB. The present study is the first to demonstrate that FABP5 expression was positively associated with progression-associated clinicopathological factors and poor prognosis in UVM, which suggests its likely function as an oncogene and prognostic marker in patients with UVM.