Objective To investigate the expression of LOXL3 gene in liver cancer tissue and its impact on patient survival using bioinformatics methods, analyze the effect of LOXL3 gene on the immune microenvironment of liver cancer, and predict the chemoresistance and immunotherapy efficacy of liver cancer. Methods The expression of LOXL3 gene in liver cancer cells was analyzed using The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. Gene Set Enrichment Analysis (GSEA) was used to analyze the possible enriched pathways of LOXL3. The relationship between LOXL3 gene expression in liver cancer patients and immune cell infiltration was analyzed using the Tumor Immune Estimation Resource (TIMER) database and TISIDB. The relationship between LOXL3 gene and chemoresistance in liver cancer was analyzed using the Genomics of Drug Sensitivity in Cancer (GDSC) database. The immunotherapy efficacy of liver cancer patients was predicted using the Tumor Immune Dysfunction and Exclusion (TIDE) database, and the impact of LOXL3 gene on patient survival was analyzed using Kaplan-Meier analysis. Results The results of both TCGA and ICGC databases showed that the expression of LOXL3 was higher in liver cancer tissue than in normal tissue, and the difference was statistically significant. LOXL3 had certain activation effects on pathways such as TGF-β, Wnt-β-Cantenin, Hypoxia, and PI3K/AKT. The level of immune cell infiltration revealed that the expression level of LOXL3 in liver cancer tissue was positively correlated with B cells (r=0.463, P＜0.05), CD8+T cells (r=0.469, P＜0.05), CD4+T cells (r=0.557, P＜0.05), macrophages (r=0.71, P＜0.05), neutrophils (r=0.528, P＜0.05), and dendritic cells (r=0.654, P＜0.05). Chemotherapy sensitivity analysis indicated that the low expression of LOXL3 gene in liver cancer tissue was resistant to chemotherapeutic drugs such as axitinib, paclitaxel, cisplatin, gemcitabine, vincristine, and vinblastine. However,in immunotherapy prediction, the low expression of LOXL3 in liver cancer patients could benefit from immunotherapy to some extent. Survival analysis showed that patients with high LOXL3 expression had a poor prognosis. Conclusion LOXL3 is highly expressed in liver cancer tissue and can activate immune-related pathways. It is sensitive to some chemotherapeutic drugs, and can benefit from immunotherapy. Therefore, it can be used as a new molecular marker for liver cancer