The role of microRNAs (miRNAs) in regulating innate immune response to Candida albicans infection in Caenorhabditis elegans is still largely unclear. Using small RNA SOLiD deep sequencing technique, we profiled the miRNAs that were dysregulated by C. albicans infection. We identified 16 miRNAs that were up-regulated and 4 miRNAs that were down-regulated in nematodes infected with C. albicans. Bioinformatics analysis implied that these dysregulated miRNAs may be involved in the control of many important biological processes. Using available mutants, we observed that mir-251 and mir-252 loss-of-function mutants were resistant to C. albicans infection, whereas mir-360 mutants were hypersensitive to C. albicans infection. The expression pattern of antimicrobial genes suggested that mir-251, mir-252, and mir-360 played crucial roles in regulating the innate immune response to C. albicans infection. Fungal burden might be closely associated with altered lifespan and innate immune response in mir-251, mir-252, and mir-360 mutants. Moreover, mir-251 and mir-252 might function downstream of p38 mitogen activated protein kinase (MAPK) or IGF-1/insulin-like pathway to regulate the innate immune response to C. albicans infection. Our results provide an important molecular basis for further elucidating how miRNA-mRNA networks may control the innate immune response to C. albicans infection.