In chronic upper respiratory tract diseases, increased cell proliferative activity is observed, which is coordinated by BCL-2 proteins and small non-coding RNAs. This study aimed to determine the expression of critical apoptosis markers at the mRNA and miRNA levels in patients with chronic rhinosinusitis with nasal polyps (CSRwNP). The study group consisted of ten patients with CSRwNP and ten healthy subjects. To detect in situ apoptosis in the maxillary sinus mucosa, TUNEL staining was performed. The expression of transcripts was determined by RT-qPCR and included the detection of markers associated with cell survival and apoptosis, i.e., BAX, p53, p21, CASP3, CASP9, c-MYC, CCND1, BRIC5, and APAF1. Levels of miR-17-5p, miR-145-5p, miR-146a-5p, and miR-203a-3p were also measured by RT-qPCR. The obtained results indicated increased apoptosis determined by a TUNEL assay in CSRwNP patients and accompanied by an increased expression of BAX, P21, P53, CASP3, CASP9, c-MYC, and APAF-1 transcripts and decreased mRNA levels of BCL-2 and BIRC5. Furthermore, the nasal sinus epithelium of patients with CSRwNP showed increased levels of miR-203a-3p while also showing a decreased expression of miR-17-5p and miR-145-5p. Our results showed that pro-apoptotic transcripts detected at mRNA and miRNA levels might be involved in the pathogenesis of chronic sinusitis with polyps. The identification of those key molecular mediators may be applicable for the specific diagnostic and/or development of targeted therapies for chronic sinusitis with polyps.