Objective To investigate renal injury, functional impairment, histopathological characteristics,and molecular features accompanying HCC development in the context of non-alcoholic steatohepatitis, utilizing a novel MASH-HCC murine model ( HRAS-HCC). This research seeks to elucidate the underlying mechanisms of MASH-HCC-induced renal injury, thereby providing an essential model tool for clinical investigations into disease pathogenesis and the exploration of diagnostic and therapeutic strategies. Methods HRAS-HCC transgenic mice generated in-house were employed, with littermate negative controls and wild-type C57BL / 6 mice as comparators. At 5 weeks of age, tamoxifen was administered to induce hepatocyte-specific HRAS expression, thereby initiating and propagating MASH-HCC. Body mass, general condition, and behavioral parameters were monitored serially during disease progression ( weeks 1 ~ 4). Blood was collected at predetermined time points for biochemical analyses.Structural and fibrotic changes in renal tissue were evaluated by hematoxylin-eosin(HE) and Masson staining. Results Compared with the HRAS^NON-TAM group, Within 4 weeks, HRAS-HCC mice transitioned from MASH through hepatic fibrosis to established HCC, manifesting jaundice, tachypnea, kyphosis, hematochezia, hepatosplenomegaly, and other clinical signs. At week 4, serum alkaline phosphatase(ALP) was significantly decreased (P<0. 05), whereas blood urea nitrogen(UREA), uric acid(UC), and creatinine(CREA) were markedly elevated (P<0. 05). HE staining revealed temporally heterogeneous renal lesions, including tubular basophilia, hyaline glomerulopathy, and tubular epithelial cytoplasmic hyaline droplet formation. Masson staining demonstrated renal fibrosis whose onset (weeks 2 ~ 3) and severity paralleled those of hepatic fibrosis/ cirrhosis(weeks 2 ~ 3). Further analysis of kidney injury-related molecular expression revealed at week 3 showed up-regulation of keratin-18, SMAD3, fibronectin, and transforming growth factor-β mRNAs ( P<0. 05 ). Protein-protein interaction analyses further indicated direct interactions among human HRAS, fibronectin (FN1), and SMAD3. Conclusions These data establish a positive correlation between MASH HCC-induced renal injury and the degree of hepatic fibrosis, clarify the attendant histopathological and molecular signatures, and implicate the HRAS-SMAD3-FN1 axis as a putative mechanistic pathway. The HRAS-HCC mouse model uniquely recapitulates key clinicopathological features of human MASH-HCC complicated by CKD, thereby providing a robust pre-clinical platform for mechanistic dissection and therapeutic development.