BACKGROUND: Alternative splicing (AS) is a regulatory mechanism used to create many forms of mature messengers RNAs (mRNAs) from the same gene. Sequencing of RNA (RNA-Seq) is an advanced technology, which has been utilized by different studies to find AS mechanisms in head and neck cancer (HNC). Hitherto, there is no available review that could inform us of the major findings from these studies. Hence, we aim to perform a systematic literature search following PRISMA guidelines to study AS events in HNC identified through RNA-Seq studies. RESULTS: A total of five records were identified that utilized RNA-Seq data for identifying AS events in HNC. Five software was used in these records to identify AS events. Two genes influenced by AS i.e. MLL3 and RPS9 were found to be common in 4 out of 5 records. Likewise, 38 genes were identified to be similar in at least 3 records. CONCLUSIONS: Alternative splicing in HNC is a multifaceted regulatory mechanism of gene expression. It can be studied via RNA-Seq using different bioinformatics tools. Genes MLL3, as well as RPS9, were repeatedly found to be associated with HNC, however needs further functional validation.