PURPOSE: To identify the inter-fractional shift pattern and to assess an adequate treatment margin in the radiotherapy of a liver tumor using mega-voltage computed tomography (MVCT) of a tomotherapy unit. MATERIALS AND METHODS: Twenty-six patients were treated for liver tumors by tomotherapy from April 2006 to August 2007. The MVCT images of each patient were analyzed from the 1st to the 10th fraction for the assessment of the daily liver shift by four groups based on Couinard's proposal. Daily setup errors were corrected by bony landmarks as a prerequisite. Subsequently, the anterior-, posterior-, right-, and left shifts of the liver edges were measured by maximum linear discrepancies between the kilo-voltage computed tomography (KVCT) image and MVCT image. All data were set in the 2-dimensional right angle coordinate system of the transverse section of each patient's body. RESULTS: The liver boundary shift had different patterns for each group. In group II (segment 2, 3, and 4), the anterior mean shift was 2.80+/-1.73 mm outwards, while the left mean shift was 2.23+/-1.37 mm inwards. In group IV (segment 7 and 8), the anterior-, posterior-, right-, and left mean shifts were 0.15+/-3.93 mm inwards, 3.15+/-6.58 mm inwards, 0.60+/-3.58 mm inwards, and 4.50+/-5.35 mm inwards, respectively. The reduced volume in group II after MVCT reassessment might be a consequence of stomach toxicity. CONCLUSION: Inter-fractional liver shifts of each group based on Couinard's proposal were somewhat systematic despite certain variations observed in each patient. The geometrical deformation of the liver by respiratory movement can cause shrinkage in the left margins of liver. We recommend a more sophisticated approach in free-breathing mode when irradiating the left lobe of liver in order to avoid stomach toxicity.