Background: Efficient cancer screening and early cancer diagnosis can significantly decrease the rate of cancer-related deaths. Currently used measures, such as tissue biopsy and radiology, have many disadvantages which can be tackled by examining analytes of liquid biopsy. Compared to conventional measures, liquid biopsy-carried cancer biomarkers are promising non-invasive screening, diagnostic, minimal residual disease monitoring, cancer burden, and detection of the cell of origin tests that give fast results with less clinical harm. Aim: This chapter discusses the key liquid biopsy analytes, namely, circulating tumor cells, DNA, exosomes, and proteins, and their use in cancer screening and early detection. Summary of the Findings: Circulating tumor DNA (ctDNA) reflects cancer-associated alterations in genome and epigenome, namely, methylation pattern. Preliminarily findings of ctDNA examination proved high sensitivity and specificity in cancer screening, early diagnosis, minimal residual disease detection, tissue of origin tracing, and treatment response and prognosis assessment. Current promising pan-cancer ctDNA-based assays understudying are CancerSEEK, Galleri test, and PanSeer test. Some cancer protein markers are clinically applied; nevertheless, they lack specificity. The multi-omics algorithm-based methods provide the best results. Cancer proteomic analysis can reveal novel effective cancer monitoring biomarkers. Exosomes are stable for a long time with homogenous size distribution and express many bioactive subcellular particles that give better understanding and easier cancer detection. Exosomal microRNA (miRNA) can provide accurate cancer diagnosis and prognosis. Despite some encouraging results, clinical use of circulating tumor cells (CTCs) remains controversial. Conclusion: These data suggest that blood-based cancer biomarkers may replace the conventional tests as effective cancer screening and early detection assays besides identifying post-diagnosis cancer characteristics.