The phenol biosorption is the best alternative to substitute or complete the current treatment forms for the elimination of phenol from the wastewater. A few phenol resistant isolates were obtained from soil specimens gathered from Jeddah, KSA. The yeast ShY-1 isolate removed 1.13 g/l of phenol, and it was considered as the highest phenol-removing isolate. It was identified as Candida tropicalis through BLAST analysis of the obtained ribosomal ITS region, then its phenol-uptake capacity was increased in relation to the induced genetic variations. The ShUV10/12 mutant was the best for phenol absorption (94%) compared to wild type strain (45.2%). The next mutant is ShUV10/7 where phenol was uptake by 90.4 % contrasted with the wild strain. Furthermore, protoplast fusion led to producing superior phenol-uptake fusants from yeast. The best phenol-uptake fusant was ShC1/3 which uptake 96.8 % contrasted with the wild strain (45.2%). Moreover, inter-simple sequence repeat (ISSR) techniques using polymerase chain reaction (PCR) on the best mutants and fusant were utilized to correspond the hereditary attributes of the best mutants and fusants with the outcomes acquired through the phenol-uptake experiments in examination with the wild strain. Furthermore, two mutants and the superior fusant comparisons with the wild strain were divided into different clusters. The phylogenetic tree was obtained and the genetic backgrounds of the selected mutants and fusant as well as the wild strain were detected according to the genetic distances.