Objective To compare the efficiency of χ~2-Fisher's exact test which is one of the competitive null hypothesis approaches with SAM-GS which belongs toself-contained null hypothesis approaches. Methods The two methods were used to analyze a simulation experiment which contained five different scenarios. The results were compared with the simulated initialization,and assessing indexes were calculated to compare the efficiency. Results Under the same conditions,SAM-GS always have higher power than that of χ~2-fisher's exact test. However, the final inference is equivalent, namely if the difference between the two groups are smaller than 0.30,the two methods can not be better to identify differences between them. By contrary, when the differences between the two phenotypes are larger than 0.30, the two ways can both identify differences. Conclusion SAM-GS tends to have slightly higher power thanχ~2-Fisher' s exact test. The two methods can be used for screening enrichment gene sets of gene expression profile.χ~2-Fisher's exact test has the important advantage of being able to analyze multi-class phenotype.