RNA-seq workflows have become progressively more efficient over time however, RNA extraction still remains a significant bottleneck. For small numbers of sample, highly efficient RNA extraction is simple to perform but becomes costly and laborious at the scale of hundreds of samples. Our prior work has demonstrated that qPCR can be accurately performed using bulk cells samples lysate instead of RNA extraction. We combined this method with the recently developed simple method for rapid RNA-seq library prep; Smart-3SEQ (Foley et al., 2019) and hypothesized that bulk RNA-seq can be performed in a multi-well plate format, and at low cost by performing RNA-seq library prep cDNA synthesis using in-lysate RNA followed by Smart-3SEQ. The result shows success of our approach in various levels: 1) all quality control measures were achieved, 2) Gene expression profiles, gene differential expression and the response patterns reported by in-lysate and purified RNA library highly correlate with each other, and 3) in-lysate RNA-seq library prep performed similar to the gold standard used here (Illumina Truseq) for DEG calling. Overall design: Human primary dermal fibroblasts from 6 donors were exposed to DMSO(vehicle), calmidazolium(10 μM)  or fludrocortisone(10 μM) for 6 hours. For purified_RNA samples, RNA extraction was done and for in-lysate RNA, cultures were treated with Igepal CA 630(0.3%)/BSA(0.1%) buffer for 5 min and supernatant was used for library prep. For both methods, cDNA libraries were prepared using Smart-3SEQ library prep and sequenced. For our gold standard, extracted RNA was used to prepare Illumina TruSeq libraries and then sequenced. Comparison is to be made between Purified_RNA and in-lysate RNA prepared with Smart-3SEQ library and how these data compare to the gold standard.