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口腔黏膜下纤维化症是口腔癌前病变的另一种，成因几乎全为嚼槟榔引起，病灶常见于颊黏膜、其次是腭部和臼齿后区，患部黏膜首先失去正常的浅红色、变白，接着反覆出现溃疡或水泡，最后黏膜会慢慢失去弹性，用手指触压可明显感受黏膜有如皮革，甚至摸到纵走方向的“纤维化带”，此纤维化带会拉住嘴角与颊黏膜，造成无法张大口，严重影响日常口腔功能，如进食、刷牙或牙齿之检查、治疗等。

病灶如果发生在口咽之间的软腭部位，可导致吞咽困难；悬雍垂也会因而萎缩或变形，用手刺激时不会有呕吐反射。临床伴随口内烧灼感、刺痛、干涩的感觉，对辛辣、热等食物极度敏感，味觉却显麻木。

病程进行到后段，可能并发喉痛、耳痛、失聪，到发展成口腔癌，则有较高的死亡率。目前治疗方式有：注射类固醇或全身性用药减少纤维化物质；手术或雷射摘除纤维化带，不过疗效有限，且多因体质而异，用药也可能有不少副作用，最好还是预防胜于治疗，拒吃槟榔即可完全预防此症。