Background: Non-alcoholic steatohepatitis (NASH) is considered an asymptomatic disease. It is well established that NASH decreases patients health-related quality of life (HRQOL). The HRQOL refers to factors of everyday living that impact medical status. Ten-items domains were selected from short form (SF-36) health survey quality of life which is more related to NASH symptoms, including fatigue, abdominal bloating, and itching, which are negatively affected in almost all aspects of the physical activity of NASH patients. Objectives: This study aimed to estimate the effect of pentoxifylline (PTX) treatment on health quality of life in NASH patients by evaluating the SF-36 health questionnaire. Patients and Methods: We designed a 6-month, open-labeled clinical trial study for 25 NASH participants. We collected the data from patients at baseline and after 6 months of treatment with PTX at 400 mg three times daily. This questionnaire was performed at Hepatology Clinic, Ain Shams University Hospital. Results: The present study showed a marked decrease in SF-36 score concerning fatigue by about (67.16%, p = 0.0001), dizziness (72.28%, p = 0.0001), shortness of breath (15.25%, p = 0.0001), loss of appetite (37.29%, p = 0.0001), legs swelling (13.44%, p = 0.0001), itching (44.44%, p = 0.0001), slurred speech (6.20%, p = 0.0078), abdominal pain (75.86%, p = 0.0001), discoloration of eye and skin (43.20%, p = 0.0001), and abdominal bloating (132.25%, p = 0.0001) after PTX treatment. Conclusion: Indeed, after 6 months of treatment, PTX significantly improved the HRQOL in NASH patients compared to baseline.