Oral cancer (OC) is the leading cause of fatalities in Pakistan among males due to inadequate oral hygiene and chewing habits. However, genetic susceptibility patterns also play a critical role in disease progression. Since the frequency of Resistin (RETN) SNP (Single nucleotide polymorphism) rs3219175 is unknown; there is a requirement for early diagnosis of the OC. Therefore, the current study aims to determine the frequency of targeted SNP and develop a safe, simple, and fast alternative technique for better treatment using a real-time PCR assay with HRM (high-resolution melting curve) analysis. A case-control study was conducted on 35 Oral squamous cell carcinomas (OSCC) diagnosed patients and 35 healthy individuals. HRM and RT-PCR results were analysed by the bioinformatics analyses. The frequency of RETN SNP rs3219175 genotypes GG and GA in male patients was 16 (46%) and 5 (14%) respectively and in females 8 (23%) and 6 (17%) respectively. The chi-square test of independence consummated the assessment between males and females in both control and patients. The relation between these variables was significant (p<0.05). The interaction network of String 8.3 demonstrates strong interactions at a high confidence score, which helps to characterize functional disorders that may be a causative factor for oral pathology. Reactome and KEGG data were acquired to rule out the pathway involvement of the targeted gene. MuPIT software was used to identify the 3D structure or RETN and their expected mutation effect. This study provides baseline data regarding the frequency of RETN SNP rs3219175 among the Pakistani population. For further clarification of their stage in cancer emergence and growth, large-scale studies must be conducted. This study might be helpful in the precision medicine approach and provide better therapeutic for OSCC patients.