Objective <p>The aim of our study was to evaluate the correlation between hepatic fat fraction (HFF) and ALT, GGT, and AST in patients with colorectal cancer after FOLFOX4 chemotherapy.</p> Methods <p>This retrospective study included 56 colorectal cancer patients who received FOLFOX4 chemotherapy and 60 non-chemotherapy patients as controls. HFF was quantified from MRI-PDFF images by placing regions of interest in eight Couinaud liver segments. Liver enzyme levels (ALT, GGT, AST) were measured from fasting blood samples. Interobserver consistency for HFF measurements was evaluated using intra-class correlation coefficient (ICC). The normality of data was assessed using the D’Agostino–Pearson test. Spearman correlation and multiple linear regression (adjusted for age, BMI, diabetes, and hypertension) were used to analyze associations between HFF and liver enzymes. Diagnostic performance of HFF was evaluated using receiver operating characteristic (ROC) curve analysis.</p> Results <p>Interobserver agreement for HFF measurements was excellent (ICC = 0.892). In the chemotherapy group, HFF showed a strong positive correlation with GGT (<i>r</i> = 0.838, <i>p</i> &lt; 0.001) and AST (<i>r</i> = 0.518, <i>p</i> &lt; 0.001). After adjustment for confounders, HFF remained independently associated with ALT (β = 1.026, <i>p</i> = 0.029), GGT (β = 13.078, <i>p</i> &lt; 0.001), and AST (β = 1.227, <i>p</i> = 0.007). ROC analysis indicated that HFF effectively predicted elevated liver enzymes: for GGT, AUC = 0.942 (cut-off: 12.275%, sensitivity 92.3%, specificity 83.3%); for AST, AUC = 0.817 (cut-off: 13.15%, sensitivity 90.0%, specificity 67.4%); for ALT, AUC = 0.789 (cut-off: 12.95%, sensitivity 90.9%, specificity 64.4%).</p> Conclusion <p>Our results suggest that HFF is correlated with ALT / GGT and AST levels in colorectal cancer patients treated with FOLFOX4 chemotherapy.</p>