The type I interferon (IFN) pathway is tightly regulated to prevent undesired consequences, such as inflammation and autoimmunity. Several regulatory mechanisms control the optimal levels of type I IFNs and proinflammatory cytokines. One such regulatory mechanism is orchestrated by small negative post-transcriptional gene regulators, termed microRNAs (miRNAs). Previous work from the group has shown that miRNAs are key players in silencing the type I IFN response in early mouse development. Herein, I aim to determine if this regulation is conserved in early human development. To do so, I characterised the type I IFN response in human cells deficient in miRNAs, by inactivating a single copy or both copies of DGCR8, a key component of miRNA maturation, using CRISPR. We show that DGCR8 regulates the antiviral innate immune pathway in a previously undiscovered non-canonical, miRNA-independent manner. While inactivating a single copy of DGCR8 did not impact the IFN pathway, the complete deletion of DGCR8 resulted in increased IFN signalling and cells being more efficient at defending against viruses. We hypothesise that this is because DGCR8-deficient cells present a constitutively activated IFN response, potentially activated by the accumulation of RNA derived from transposable elements, which is usually silenced by epigenetic mechanisms. When transcribed, these repetitive elements can form double-stranded RNA (dsRNA) structures that are detected by the antiviral nucleic acid sensors, leading to constitutive activation of the IFN pathway in the absence of a virus. In conclusion, we show that miRNAs are important regulators of the type I IFN pathway not only by regulating the expression of specific proteins involved in nucleic acid sensing and signalling, but also by preventing the accumulation of dsRNAs that can be aberrantly recognized by the innate immune system as foreign. All these processes together lead us to predict that human diseases characterised by miRNA imbalance may also display aberrant IFN activation.