MicroRNAs are small non-coding RNAs that post-transcriptionally regulate expression of many genes. MicroRNA activity is essential for animal development as alterations in microRNA expression and function have been associated with many developmental pathologies and diseases, making microRNAs of great interest as diagnostic and therapeutic targets. However, little is known about how microRNA function itself is modulated by specific developmental and physiological signals. We wish to understand how cellular factors may integrate these signals to modulate microRNA-mediated gene repression. Using proteomics approaches, we identified a conserved yet uncharacterized RNA binding protein, HRPK-1, as an Argonaute ALG-1 interacting factor. Loss of hrpk-1 function results in a number of developmental phenotypes, including defects in embryonic development, fertility, and organ morphogenesis, all phenotypes reminiscent of defects seen in specific microRNA mutants. Knockdown of hrpk-1 by RNAi enhances the embryonic lethality associated with mir-35-41 mutants, suggesting that hrpk-1 function is required at least for miR-42 activity. RNAi knockdown of hrpk-1 also enhances the cell fate defect observed in a reduction-of-function allele of a neuronal microRNA, lsy-6, implying that hprk-1 similarly normally promotes lsy-6 microRNA activity. Interestingly, hrpk-1 mutants showed no reduction in mature microRNA production, suggesting that HRPK-1 function may not be required for microRNA biogenesis. Because HRPK-1 has predicted RNA binding domains and appears to function downstream of microRNA biogenesis, we hypothesize that HRPK-1 may modulate microRNA activity by interacting with miRISC on target mRNAs.