Aseptic loosening (AL) of artificial hip joints is the most common complication following hip replacement surgery. In the present study, second-generation high-throughput sequencing and mass spectrometry techniques were used to detect differentially expressed genes, proteins and metabolites in samples. These were further analyzed using software such as Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. Key gene, cytokine receptor-like factor-1 (CRLF1) and glutathione-S transferase μ-1 (GSTM1) expression levels were verified through reverse transcription-quantitative PCR and western blotting. The integrated transcriptomics, proteomics and untargeted metabolomics analyses revealed characteristic metabolite changes (biosynthesis of guanine, L-glycine and adenosine) and protein changes (CRLF1, GSTM1) in AL, which are primarily associated with amino acid metabolism and lipid metabolism. In summary, the current study may uncover the underlying mechanisms of AL pathology and provide stable and accurate biomarkers for early warning and diagnosis of the disease.