The messenger RNA 3’-untranslated region(3’UTR)plays an important role in regulation of gene expres-sion on the posttranscriptional level. The 3’UTR con-trols gene expression via orchestrated interactionbetween the structural components of mRNAs(cis-ele-ment) and the specific trans-acting factors(RNA bind-ing proteins and non-coding RNAs). The crosstalk ofthese factors is based on the binding sequences and/or direct protein-protein interaction, or just functionalinteraction. Much new evidence that has accumulatedsupports the idea that several RNA binding factors canbind to common mRNA targets: to the non-overlappingbinding sites or to common sites in a competitive fash-ion. Various factors capable of binding to the sameRNA can cooperate or be antagonistic in their actions.The outcome of the collective function of all factorsbound to the same mRNA 3’UTR depends on manycircumstances, such as their expression levels, affinity to the binding sites, and localization in the cell, which can be controlled by various physiological conditions. Moreover, the functional and/or physical interactions of the factors binding to 3’UTR can change the character of their actions. These interactions vary during the cell cycle and in response to changing physiological condi-tions. Abnormal functioning of the factors can lead to disease. In this review we will discuss how alterations of these factors or their interaction can affect cancer development and promote or enhance the malignant phenotype of cancer cells. Understanding these altera-tions and their impact on 3’UTR-directed posttran-scriptional gene regulation will uncover promising new targets for therapeutic intervention and diagnostics. We will also discuss emerging new tools in cancer di-agnostics and therapy based on 3’UTR binding factors and approaches to improve them. The 3 ’UTR trans-trols gene expression via orchestrated interaction between the structural components of mRNAs (cis-ele -ment) and the specific trans-acting factors (RNA bind-ing proteins and non-coding RNAs). The crosstalk of these factors is based on the binding sequences and / or direct protein-protein interaction, or just functionalinteraction. Much new evidence that has accumulated supports the idea that several of the RNA binding factors canbind to common mRNA targets: to the non-overlapping binding sites or to common sites in a competitive fash-ion. Various factors capable of binding to the same RNA can cooperate or be antagonistic in their actions. outcome of the collective function of all factorsbound to the same mRNA 3’UTR depends on many circularities, such as their expression levels, affinity to the binding sites, and localization in the cell, which can b e controlled by various physiological conditions. Moreover, the functional and / or physical interactions of the factors binding to 3’UTR can change the character of their actions. These interactions vary during the cell cycle and in response to changing physiological condi- tions. Abnormal functioning of the factors can lead to disease. In this review we will discuss how alterations of these factors or their interaction can affect cancer development and promote or enhance the malignant phenotype of cancer cells. Understanding these altera- tions and their impact on 3’UTR -directed posttran-scriptional gene regulation will uncover promising new targets for therapeutic intervention and diagnostics. We will also discuss emerging new tools in cancer di-agnostics and therapy based on 3 ’UTR binding factors and approaches to improve them.