Entrained and reset by external cues, the circadian clock controls physiological processes, including liver metabolism. At the cellular level the clock is characterised by core clock genes, which modulate the fluctuating expression of central metabolic genes as transcription factors. Being an extensive biological process, the clock is linked to the elements of cell cycle control and intracellular signalling pathways. Recent analyses identified the liver clock also to be associated with the hedgehog (HH)-signalling, an evolutionary conserved cascade functioning as crucial modulator of embryogenesis and tissue differentiation. Although there is an evidence of its role in adult liver, no exact mechanisms are known. Our aim was, therefore, to analyse the liver specific interaction of the HH-signalling and the circadian clock, using the transgenic knock-out mice, displaying a hepatocyte specific deletion of Smo (Smo-KO), an essential transducer within the HH-signalling. Mice (male, 10-12 weeks, 19-25g) were maintained under controlled conditions (12:12 h LD-cycle, fed ad libitum) and at different time-points, animals were anesthetised with a mixture of ketamine (100mg/kg), rompune (5 mg/kg) and atropine (0.1 mg/kg). Further, the RNA was extracted either from whole livers or collagenase-perfused isolated hepatocytes. We performed gene microarray analyses, comparing KO- mice and their WT-littermates, considering the different circadian time-points of hepatocyte isolation. The data were classified according to the GO clusters and evaluated using the ANOVA statistical analyses. Generally, due to hepatic Smo deletion the results show strong alterations in the circadian expression levels of genes involved in metabolic and transport processes (e.g. Smo-WT:179 vs. Smo-KO:234 genes are up-regulated, n=3/genotype). However, these alterations seem not to provide a significant effect on the global scale (P=0.175). In contrast, especially the circadian rhythm of the lipid metabolism is significantly affected by inactive HH-pathway (e.g. Smo-WT:39 vs. Smo-KO:30 genes are up-regulated, whereby only 17 genes are common for both genotypes, P=0.001). Verified by qRT-PCR analyses, some core clock genes exhibit strong alterations in their expression due to Smo-KO (e.g. level of Per3 is elevated at 09:00 to a factor 2.7±0.5, P=0.007; Per1 – to a factor 1.7± 0.2, P=0.5; n=6-10; values are means ±S.E.M.). A putative transcription factor binding site prediction, generated using Fantom4 database, allows us to conclude that in adult liver the HH signalling seems to be closely related to the circadian clock and, thus, might be involved in the regulation of the rhythmicity of lipid metabolic processes. However, the precise function of HH-signalling within the clock regulatory circuit still has to be evaluated, requiring further investigations.