A 79-year-old woman, who had been treated because of mixed connective tissue disease (MCTD), was admitted to the hospital for the intensive examination of a hepatic tumor that was unexpectedly found on computed tomography. The hepatic tumor was approximately 40 mm in diameter. Her transaminase levels were slightly elevated but hepatic virus markers were negative. However, a liver aspiration biopsy revealed moderately differentiated hepatocellular carcinoma (HCC). In the surrounding non-tumor area, nonspecific reactive hepatitis was detected. MCTD associated with HCC has not yet been reported in the past. This case appears to be very interesting in terms of the etiology of HCC.