Objective To construct a prognostic model for fatty acid catabolism(FAC)related genes and validate the role of ABHD1 and PLA2G15 in colorectal cancer.Methods The FAC related gene set was obtained from GSEA.RNA sequencing data and clinical information of colorectal cancer were downloaded from TCGA.We performed differential expressed analysis for FAC related genes between tumor and normal samples.Univariate Cox regression analysis was used to screen differential expressed genes associated with prognosis,and then LASSO regression was utilized to further analyze and screen target genes to establish a prognostic model.The prognostic model was validated by an external dataset(GSE39582).Finally,the biological functions of ABHD1 and PLA2G15 in colorectal cancer cell lines were validated using CCK-8,colony formation,and cell cycle assays.Results Through previous analyses,5 genes(ABHD1,ACOX1,CPT2,HADH,and PLA2G15)among 102 FAC related genes were selected to construct a risk scoring prognostic model.Patients with high-risk scores had a worse prognosis compared to those with low-risk scores.Multivariate Cox regression analysis showed that the prognostic model was an independent prognostic factor.The external dataset(GSE39582)also validated the effect of this prognostic model evaluating prognosis.We conducted experimental validation for these two genes.The experimental results indicated that ABHD1 and PLA2G15 had impacts on promoting the proliferation of colorectal cancer cells in vitro.Conclusion The FAC prognostic model has a predictive effect on the prognosis of colorectal cancer patients.ABHD1 and PLA2G15 may have a certain promoting effect on the growth of colorectal cancer,which deserves further research.