Clostridium difficile is a pathogenic bacterium causing antibiotic-induced diarrhoea in the immuno-compromised. Genomes of the majority of C. difficile strains encode inducible prophages that could access the lytic pathway in a susceptible host. Although C. difficile phages with lytic ability have been characterised in literature, knowledge of the impact they exert on their hosts is limited. Previous studies revealed that the phages could transduce infected cells, influence toxin production and regulate phase variable genes during lysogeny. However, no studies currently exist to reveal the global transcriptional response of C. difficile during a phage lytic infection cycle. Here, we determined the lytic growth kinetics of phiCDHS1, a siphovirus infecting the R20291 strain and analysed the genes expressed during the phage cycle. Analysis of the one-step growth curve revealed that the phage completes its replication in 30 min with a burst size of 100. The early-log, mid-log and stationary phases of the phage replication were observed at 10, 20 and 30 min respectively. Total RNA extracted at these time points was rRNA-depleted and sequenced using Illumina HiSeqTM4000 technology. Analysis of the mapped transcripts against the reference bacterial genome suggests that 1060/3570 (~30%) genes were differentially expressed during the phage infection cycle. Phased gene expression was observed in the phage. The phage genes expressed (19/53) at 0-10 min post-infection correspond to early transcripts associated with DNA replication but the 21/53 differentially expressed genes at 20 and 30 min correlated to late transcripts for structural proteins. Analysis is currently ongoing to determine how expressions of these phage genes affect gene expression in the host bacterium. These findings will help to elucidate the transcriptional response of C. difficile to phage infection.