A randomized clinical trial was carried out to compare between conventional silicone-based soft liner and Versacryl lining material for the relining of mandibular complete dentures in flat mandibular cases regarding oral health related quality of life and tissue keratinization index. Twenty-eight patients were distributed randomly into two groups (fourteen per group). After taking the relining impression for their existing mandibular dentures, the control group received conventional silicone based soft liner, while the intervention group received Versacryl lining material. Patients were evaluated at two weeks, two months and four months intervals. The results showed a significant difference between the two groups at two weeks and two months as the Versacryl relined dentures provided a better improvement in oral health related quality of life, while at four months there was no difference between the two groups. This study also showed a significant difference in parakeratization activity between the two groups at all follow up periods with the highest mean score in the Molloplast-B liner group.